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142 Cards in this Set
- Front
- Back
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what does penetrance mean?
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% of people carrying an autosomal dominant gene and also expressing the trait
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what is variable expressivity?
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variety of different problems from patient to patient with same autosomal dominant disease
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what is pleotropism?
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multiple end effects of a single mutant gene
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what is genetic heterogeneity?
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production of a given trait by different mutations
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what are autosomal dominant diseases?
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they affect structural and regulatory proteins. 50% inhereitance. onset of symptoms may occur later in life
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what is marfan's syndrome?
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fibrillin defect in skeleton, eyes, cardiovascular system
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what knid of mutation is involved in marfan's syndrome?
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missense, producing abnormal fibrillin
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what are the skeletal abnormalities seen with marfan's syndrome?
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tall, long extremities
lax ligaments caved in, or pigeon breast chest |
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what are the eye abnormalities seen with marfan's syndrome?
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bilateral subluxation or dislocation of the lens
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what are the cardiovascular abnormalities seen with marfan's syndrome?
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mitral valve prolapse and aneurysm of the assending aorta
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What is achondroplasia?
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short limbs
dwarfs large head most patients have no family history (new mutants) |
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What is huntington's disease?
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progressive dementia and choreic (abnormal) movements
usually occurs after 40+ yrs |
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which disease has a reduced penetrance, variable expressivity with at least 5 loci that cause the problem. Found on gene 7q21.3-q22.1
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split hand split foot
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what is apert's syndrome?
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all new mutations
syndactyly (sock hands and feet) premature closure of the cranial sutures (craniosynostosis) mutation of fibroblast growth factor receptor 2 |
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what is tuberous sclerosis?
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chromosome 9 and 16 problems
seizures retard sebaceous adenomas on skin leathery thickenings in local patches hypopigmentation subungual fibromas angiomyolipoma |
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what is the difference between autosomal dominant and recessive disorders?
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recessive- more, onset is earleir, enzymes most effected, complete penetrance, expression is more uniform
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what is phenylketonuria?
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don't make the enzyme phenylalanine hydroxylase. Causes hyperphenylalaninemia leads to mental retardation
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why do doctors test babies for phenylketonuria?
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because it can be prevented with a very strict diet that doesn't have phenylalanine in it
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what common diseases are often seen in association with lysosomal storage diseases?
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hepatomegaly
splenomegaly due to lysosomes becoming filled with macromolecules and normal cell function is inhibited |
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what causes tay sach's disease?
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deficiency in hexosaminidase A, therefore GM2 ganglioside accumulates in the tisues
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who is most likely to get Tay sachs and what are the distinguishing characteristics seen with it?
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jews from eastern europe
cherry red spot in retina whirling neurons ballooning of neurons |
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what happens to those effected with tay sahcs?
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blind
motor and mental deterioration by 6months of life death by age 2-3 |
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which lysosomal disease has a deficiency with hexosaminidase B?
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sandhoff disease
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What is the dificeiency seen with niemann pick disease?
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sphingomyelinase, whicj leads to too much sphingomyelin
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what are the characteristics of the two types of niemann pick disease?
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A-infantile, death within first 3 yrs
B-no CNS involvement, later in life, usually has organomegaly |
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What is the most common lysosomal disorder?
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gaucher's disease
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what is the enzyme deificeincy seen with gaucher's disease?
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glucocerebrosidase
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what are the 3 types of gaucher's?
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I- adults, fractures, splenomegaly, shortened lifespan
II- infantile, CNS inolved, early death III- juvenile, progressive CNS involvement, shorten lifespan between types I & II |
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what does the cytoplasm look like in gaucher's disease?
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fibrillary appearance, like a crumbled piece of tissue paper, PAS positive
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What enzyme is eficient in krabbe's disease?
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galactosylceramidase
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What is the toxic product in krabbe's disease?
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psychosine, a metabolite of galactocerebroside
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what happens to the body with krabbe's disease?
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myelin and oligodendrocytes are lost, and macrophages fill with the cerebroside. usually dead by age 2
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what is the deficiency seen with metachromatic leukodystrophy?
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arylsulfates A
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what type of disease is adrenoleukodystrophy?
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X-linked
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What are mucopolycaccharidosis?
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defiencies of lysosomal enzymes that degrade mucopolysaccharides
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what type of diseases are the mucopolsaccharidosises?
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Autosomal recessive (except Hunter's, which is X-linked)
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what are the characteristics seen with mucoploysaccharidoses?
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coarse facial features
clouded cornea joint stiffness retard |
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describe hurler's syndrome
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deficiency of alpha-L-iduronidase, which causes dwarfism
develops by 6-24 months |
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describe hunter syndrome
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x-linked recessive
deficiency in L-iduronate sulfatase |
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what are the two forms of glycogen storage diseases?
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hepatic- no G-6-phosphatase, leads to hypoglycemia and hepatomegaly
myopathic- glycogen stored in muscles, leads to muscle cramps and no lactic acidosis from excercise |
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what is Pompe's disease?
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glycogen storage disease seen in many organs
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what is alkaptonuria?
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no homogentisic acid oxidase, which blocks the metabolism of phenylalanine
black urine eroded cartilage |
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What is Rett syndrome?
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lethal in males, retarded and sterile girls. X-linked dominant
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what is vitamin D resistant Rickets?
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renal tubular loss of phosphte which interferes with skeletal ossification
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what is the x-linked recessive disorder lesch-nyhan syndrome?
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no HGPRT, which normally picks up purine bases.
Leads to increased uric acid production self mutilation and retards no dopaminergic terminals and cells gout |
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what results from combined actions of environment and two or more mutant genes?
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multifactoral inheritance
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what are some examples of multifactoral inheritances?
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chance of expressing increases with number of mutant genes
congenital heart disease diabetes cleft lip hypertension gout |
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what are cytogenetic disorders?
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aterations in the number or structure of the chromosomes
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what ususally happens with monosony of an autosome?
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loss of too much genetic material for a live birth
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what is mosaicism?
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two or more populations of cells in the same individual
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what is translocation?
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segments of the chromosome are transferred to another
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what are inversions?
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two breaks in one chromosome that rearranges
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what is a ring chromosome?
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terminal ends are lost
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what are isochromosomes?
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chromosome where one arm is missing and the other is duplicated
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what is the most common chromosomal disorder?
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trisomy 21 (downs syndrome)
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what is the percentage of affected individuals with trisomy with a chromosome count of 47?
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95% (meiotic nondisjuction)
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How can the mother have an effect on Trisomy 21?
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maternal age over 35 increases the risk of trisomy 21.
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what characteristics are seen with Trisomy 21?
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flat face
retard congenital heart disease increased risk of leukemia simian crease- only one skin fold on her hand |
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what is the median age of death for trisomy 21?
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47
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what characteristics are seen with Patau's syndrome (trisomy 13)
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microcephaly
micropthalmia retard rocker bottom feet polydactyly meiotic nondisjunction |
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What is Cri-du-Chat syndrome?
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deletion of 5p
retard cat-like cry |
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what is the disease that has atleast 2 X chromosomes and at least 1 Y chromosome and also has hypogonadism?
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klinefelter syndrome
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what is the principle cause of reduced spermatogenesis and male infertility?
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klinefelter's syndrome
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What are the characteristics of klinefelter's syndrome?
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High FSH and estrogen, low testosterone
long limbs gynecomastia |
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what sex linked chromosome abnormality still appears normal and tall?
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XYY syndrome
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What disease has peripheral lymphedema at birth, conginital heart disease, webbed feet, short stature, with spaced apart nipples?
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Turner Syndrome
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What kind of chromosome abnormality is seen with turner's syndrome?
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complete or partial monosomy of the X chromosome
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what autoimmune disease is a higher risk of developing when a patient has turner syndrome?
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autoantibodies against the thyroid
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what disease has a defect in the synthesis in the fibrillar collagen and typically involves the skin and joints?
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Ehlers-Danlos syndrome
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what disease starts with a genotype male, but because of a mutation in the androgen receptor gene they become phenotype females when estrogen takes over, but lack ovaries and a uterus, and usually have testicles within the abdomen or the inguinal canal?
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androgen insensitivity
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what disease has multiple tandem repeats of CGG?
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fragile X syndrome
up to 29 repeats is normal up to 200 is premutation over 200 is bad has an enlarged testes elongated face large everted ears |
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what is the difference between fragile x syndrome from genetic and inherited?
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males is the carrier, it affects females
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what are the 3 characteristics that define a tissue as neoplastic?
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exceeds and is uncoordinated with the normal tissue areound it
persists after the stimuli which provoked it is removed oblivious to normal contrl mechanisms and replication |
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what two components do all tumors, both benign and malignant have in common?
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they both have parenchyma and supporting tissue
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what does the suffix -oma normally mean?
what are the 3 common exceptions? |
benign
melanoma, seminoma, hamartoma |
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what does a name like carcinoma tell us about the tissue of origin?
sarcoma? lymphoma? leukemia? |
epithelial tissue
mesenchymal (germ layer) lymphoreticular hematopoetic |
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how does differentiation paly a role in the malignacy or benign level of a neoplasm?
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the more differenciated the cells are, or the closer that the neoplastic cells are to that of the tissue of origin, both morphologically and functionally, the more benign the tissue is
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what does anaplasia mean?
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a lack of differentiation
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what changes are often seen histologically with anaplastic cells?
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cellular and nuclear pleomorphism
nuclear hyperchromasia (stain dark) bigger than normal nulei organisation inside cells doesn't resemlbe tissue around them giant tumor cells present |
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what is the difference between anaplasia and dysplasia?
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dysplasia does have pleomorphism like anaplasia with the loss of orientation, but they don't indicate cancer, and usually means the growth is confined to the tissue of origin
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how does the rate of growth help us distinguish between benign and malignant?
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both grow slowly, but malignant tend to grow a little faster
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how does the local invasion of the surrounding tissue help us distinguish between a malignant and a benign tumor?
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benign- derived from stroma of native tissue and are cohesive and well defined
malignant- infiltrative growth, destruction of surrounding tissue, very undefined edges |
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if a tumor is metastatic, is it benign or malignant?
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malignant
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what are the 4 ways that tumors spread to other parts of the body?
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- seeding of body cavities
- lymphatics - hematogenous - tissue or blood transplant |
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why are tumor cells easily triggered into the cell cycle?
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because they have defective cell cycle controls, like Rb and p53
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how large can tumors become before they rely on their own vascularization?
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1-2mm
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how do tumors develop a blood supply?
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they undergo an "angiogenic switch" and more proangiogenic factors are produced than antiangiogenic factors by either the cell itself, or by inflammation response by cells around it.
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what happens to the monoclonal malignant tumors as they become alrge enough to be clinaccly evident?
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they have become heterogenous, with some cell types being more metaplastic than others, perhaps more resistant to chemotherapy, and with a greater invasive potential
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why do monoclonal tumors become heterogenous?
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because they are genetically very unstable, with a high rate of random mutations
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what is the difference between tumor invasion and dissemination?
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invasion- cells detach from one another and attach to the matrix, degradres the ECM and basment membrane and migrates
dissemination- same but migrates into a vessel where it forms an emboli and can adhere to the vessel wall |
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what are the main difference between grading and staging tumors?
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grading is based on degree of differentiation, but it is inexact and subject to observer bias
staging determines the size, extent of spread, and presence of metastasis of the tumor and does not really have a problem with observr bias |
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why is staging helpful?
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allows communication between different medical teams and it is specific to the patient but allows a basis of comparison
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what are the two staging systems?
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UICC- uses T(size) M(metastasis) and N (lymph node envolvement)
AJC- uses numerical 0-4, 4 being the most malignant |
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what kind of damage to cell leads to carinogenesis?
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non-lethal genetic damage
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what is the difference between proto-oncogenes and oncogenes?
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proto- normal cell genes that control the growth and differentiation of a cell
oncogeones- associated with neoplastic formation, no longer regulating the cell the way they should |
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what are the 7 changes essential to become a malignant phenotype on a genetic level
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1- self sufficient with growth signals
2- Not affectd by growth inhibitors 3- no apoptosis 4- unlimited replication potential 5- angiogenesis 6- invasion and meastatic 7- genomically unstable |
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what products do oncogenes produce?
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growth factor
growth factor receptors signal transducing proteins nuclear transcription factors cylcin kinases |
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What are Ras proteins? What happens if they are mutated?
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a protein that regulates how how much transcription a cell undergoes by disactivating the cell from the outside signal. If it is mutated it may not be able to perform its job anymore and the cell transcribes unchecked
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what are the 3 factors that change proto-oncogenes to oncogenes
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point mutations (Ras)
translocations (being too close to a promotor or enhancer in the genome) gene amplification |
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what are the traditional tumor suppressor genes?
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p53
Rb |
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what are "caretakers"
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ensure the integrity of the genome
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why are the tumor repressor genes called autosomal dominant when it requires both of them to be mutant?
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it increases the risk of developing malignancy with just one mutated gene
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what is the difference between a familial Rb mutation and a sporatic mutation?
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familial- one is already mutant and only requires one change
sporatic- requires 2 changes |
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what gene has been deleted in over 70 percent of colon cancer patients?
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TGF-beta
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what growth inhibitory factor binds to the cell surface to inactivate it from growing, and is often found to have been damaged with patients with breast cancer?
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BRCA-1
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what enzyme is related to the signal transduction associated with the Ras molecule and without it, leads to uncontrolled growth?
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NF-1
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how does the level of phosphorylation of the Rb molecule effect its eficacy?
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the more phoshphorylated it is, it binds to transcription factors and prevents DNA synthesis
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what is the role of TP53 in the cell normally?
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it is the gaurdian of the genome, it stops the cell in G1 when there is damage and allows the cell to repair itself before the cell continues with its replication
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what are the genes that regulate apoptosis?
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BCL2
BAX |
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how d BCL2 and BAX work?
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they are usually in equilibrium.
<BCL2 = normal cell function <BAX = apoptosis |
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about how many times can most human cells replicate?
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60-70 times- due to the shortening of the telomeres
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how do tumors avoid the shortening of the telomere?
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activate the enzyme telomerase that maintains normal telomere length
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how do diseases of the breast present themselves?
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palpable mass
inflammed lession nipple discharge mammogram abnormality |
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what kind of tissue is found in the areola, the nipple, ostia of main lactiferous ducts?
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stratified squamous tissue
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what two layers are found in the major and distal ducts?
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inner- cuboidal epithelium
outer- myoepithelium |
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what differences are seen in intralobular and interlobular breast tissue?
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intra- delicate loose myxomatous stroma, lymphocytes
inter- dense dibrous connective and adipose tissue |
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what is a supernumery nipple?
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extra nipple somewhere along the mile line from the axilla to the perinium and it can be effectd by same disorders and is occasionally responsive to cyclic hormonal change
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what is accessory axillary breast tissue?
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extended breast tissue into the axillary fold.
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what is a congenital inversion of a nipple suggest?
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nothing, but it could be confused with an aquired retraction due to cancer or inflammation
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what is the differnce between acute and periductal mastitis?
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acute- usually during postpartum period, cracks and fissures in nipples, usually a staph or strep infection
periductal- associated with smoking, keritinized epitihilium extends too far into the ducts, causes chronic granulation, fibrous scarring, nipple inversion, leads to a fistula opening at edge of areola |
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what is mammary duct ectasia?
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poor deifined subareola in 50-60 yrs. thick, cheesy discharge, granulomatous inflammation
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what is characteristic of a fat necrosis in the breast?
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well-demarcated, bright yellow, usually with trauma or surgery and is often seen with calcifications, benign
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what is the most common disorder of the female breast and normally manifests between the ages 20-40?
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fibrocyst
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what breast disease is characterized by an increased number of acini per lobule, are generally hard, usually have distorted acini?
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sclerosing adenosis
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what is epithelial hyperplasia?
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more than 2 cell layers, cells fill up the lumen, forming slit like spaces
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what is the difference between DCIS and Atypical epithelial hyperplasia?
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DCIS is malignant
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how does a risk of malignancy increase with fibrocystic changes to the breast tissue?
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risk increases with sclerosing adenosis, moderate epithelial hyperplasia, and small duct papillomas, and is greatly increased when the epithelial hyperplasia is atypical
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what is the most common type of benign neoplasm in breast tissue?
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fibroadenoma
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when is a fibroadenoma most commonly found?
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reproductive age, but can be found at any age
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which tumor is leaf-like and is usually found in woman over the age of 60, is well circumscribed, and the stroma usually overgrows the epithelium, is usually benign but can be malignant?
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phyllodes tumor
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what is the most common cause of a bloody nipple discharge?
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large duct papillomas
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what does DCIS and LCIS stand for?
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ductal and lobular in-situ carcinoma
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what is the most common type of malignant breast cancer?
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ductal invasive carcinoma
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where is carcinoma of the breast most commonly found?
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upper outer quadrant of the left breast
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what factors lead to an increase of estrogen production and can attribute to cancer?
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long reproductive life, first child past 30 years, post-menopausal obesity,null aparity, high dose of exogenous estrogen, functinal ovarian neoplasm
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what is BRCA?
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a tumor suppressor gene in breast tissue
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what are the chances of developing cancer if you have a mutated BRCA1 gene and a familial history of it?
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breast cancer-85%
ovarian- 60% |
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how do you treat a ductal carsinoma in-situ
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biopsy, 10% chance of recurrence with low grade
40% with high grad comedo lesions |
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what are the odds of an invasive cancer forming from a lobular carcinoma in-situ?
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25-30% either breast
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which type of cancer tends to be "gritty" when you cut into it?
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invasive ductal carcinoma
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how does the grading system for breast cancer work?
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differentiation I-III (higher is poorly defined) and numerical 3-9 depending on mitotic count per 10hpf, nuclear size and shape, and tubular formation (higher number is worse)
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which type of cancer is seen as uniform cells infiltrating in strands, cords, and as single cells within the firous stroma?
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invasive lobular carcinoma
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