Cancer Genetics Ii

Front 1

Tamoxifen may cause increased risk of what cancer?

Back 1

uterine

Front 2

Aromatase inhibitors as treatment/prevention of breast cancer are only effective for whom?

Back 2

post-menopausal women

Front 3

Lifetime cancer risks for men and women with Li-Fraumeni

Back 3

women=90%
men=70%

Front 4

What childhood cancers are the hallmark sign of Li-Fraumeni? What is the most predictive tumor of the syndrome?

Back 4

childhood sarcomas of any type
childhood adrenocortical tumors

Front 5

Features of Cowden syndrome

Back 5

macrocephaly
trichilemmomas and papillomatous papules
breast, follicular thyroid, and uterine cancers
Llermitte-Duclose disease--benign brain tumor--hydrocephalus?

Front 6

Benign tumors associated with Cowden syndrome

Back 6

papillomatous papules
trichilemmomas
thyroid lesions
hamartomatous intestinal polyps
lipomas
fibromas of uterine, breast, etc.

Front 7

Cancers assoc. with HNPCC

Back 7

early-onset colon cancer, endometrium, ovary, small bowel, stomach, pancreas, ureter, renal pelvis

Front 8

What type of thyroid cancer is associated with FAP?

Back 8

papillary thyroid cancer

Front 9

Cancers assoc. with FAP

Back 9

adenomatous polyposis, colorectal cancer, papillary thyroid cancer, gastric cancer, periampullary carcinoma, adrenal cancer, hepatoblastoma and extracolonic manifestations

Front 10

Features of Gorlin syndrome

Back 10

basal cell nevi, characteristic facies, palmar and plantar pits, odontogenic keratocysts, rib abnormalities, increased risk of basal cell carcinoma, ovarian carcinoma, ovarian fibromata

Front 11

Genes assoc. with Li-Fraumeni

Back 11

p53, CHEK2

Front 12

Cancers assoc. with Peutz-Jehgers

Back 12

breast cancer, benign ovarian tumors, testicular tumors, pancreatic cancer, hamartomatous polyps of ureterm, GI tract, bladder, renal pelvis, bronchus, nasal passage. Melanin spots on lips, inside mouth, and on digits

Front 13

Genes assoc. with Peutz-Jeghers

Back 13

STK11, LKB1

Front 14

Findings of von Hippel -Lindau

Back 14

Hemangioblastomas of brain, retina, spine; pheochromocytomas, renal cell carcinoma, epididymal cystadenoma, endolymphatic sac tumors

Front 15

Findings of MEN2A

Back 15

medullary thyroid carcinoma
pheochromocytoma
parathyroid tumors/parathyroid hyperplasia

Front 16

Findings of MEN2B

Back 16

early-onset medullary thyroid carcinoma
early pheochromocytoma
mucosal neuromas
Marfanoid habitus

Front 17

other cancers associated with RB1

Back 17

sarcoma, lung

Front 18

Genes assoc. with juvenile polyposis syndrome

Back 18

SMAD4/DPC4

Front 19

Carcinoma is cancer of what type of tissue?

Back 19

endoderm or ectoderm-derived epithelial or skin tissue

Front 20

What % of germline retinoblastoma cases have a family history?

Back 20

20%

Front 21

Penetrance of retinoblastoma

Back 21

90%

Front 22

Cowden syndrome--lifetime risk of breast cancer

Back 22

25=50%

Front 23

Cowden syndrome--lifetime risk of thyroid cancer

Back 23

10%

Front 24

Cowden syndrome--lifetime risk of uterine cancer

Back 24

5-10%

Front 25

What is the Founder mutation of CHK2, and where is this most common?

Back 25

1100delC
Netherlands and Finland

Front 26

Findings of Proteus syndrome

Back 26

connective tissue nevi
disproportional overgrowth
lipomas or absence of fat
vascular malformation
facial phenotype

Front 27

Name 2 low-penetrance breast cancer genes

Back 27

ATM
CHK2

Front 28

Of hereditary ovarian cancer, what % is due to BRCA1?
BRCA2?
HNPCC?
other single genes?

Back 28

BRCA1=70%
BRCA2=20%
HNPCC-2%
other=8%

Front 29

Risk factors for colorectal cancer

Back 29

aging
personal history of colorectal cancer or adenomas
high fat, low fiber diet
inflammatory bowel disease
family Hx
hereditary colon cancer syndromes

Front 30

Up to what percent of people with FAP have de novo germline mutations?

Back 30

30%

Front 31

FAP--do most families have unique mutations, or the same few?

Back 31

unique

Front 32

In FAP, where else might patients have tumors?

Back 32

upper GI, desmoid, osteoma, thyroid, brain, hepatoblastoma

Front 33

Features of Gardner syndrome

Back 33

FAP plus desmoid tumore, CHRPE, osteomas, extra teeth, soft tissue skin tumors

Front 34

Features of Attenuated FAP

Back 34

later onset-50s
few colonic adenomas--more than 20, less than 100
no CHRPE
may have upper GI lesions
5' and 3' end mutations in APC

Front 35

Clinical management for FAP

Back 35

annual colonoscopy until polyposis
colectomy
annual upper endoscopy
chemoprevention
monitoring for desmoids, etc.
genetic testing for others in family

Front 36

chemoprevention for FAP

Back 36

Celebrex, Sulindac, others

Front 37

The founder FAP mutation in Ashkenazi Jews

Back 37

I1307K

Front 38

Why is the AJ founder FAP mutation (I1307K) controversial?

Back 38

Some report no increased risk

Front 39

Average age of recessive MYH-associated colon cancer

Back 39

50s

Front 40

How many polyps usually present with recessive MYH-associated colon cancer?

Back 40

more than 15, but not THAT many

Front 41

2 common MYH mutations causing recessive colon cancer.
What population gets these?

Back 41

Y165C
G382D
European

Front 42

Of all colon cancer, what % is caused by HNPCC?

Back 42

about 2%

Front 43

Extracolonic cancers assoc. with HNPCC

Back 43

endometrial, stomach, ovarian, pancreas, ureter, renal pelvis, biliary tract, glioblastoma (Turcot), keratoacanthomas (Muir-Torre), sebaceous gland adenomas

Front 44

Risk of colorectal cancer in HNPCC

Back 44

70%

Front 45

Risk of endometrial cancer in HNPCC

Back 45

43-60%

Front 46

Name the Amsterdam criteria for HNPCC.

Back 46

3 or more relatives with verified CRC in family
one case in a first degree relative of the other 2 cases
2 or more generations affected
One CRC by age 50
FAP excluded
*Failure to exclude does NOT exclude HNPCC*

Front 47

Revised Bethesda guidelines for HNPCC: MSI testing should be done when 1 or more of what guidelines exist?

Back 47

1. CRC in pt under 50
2. Presence of 2 CRCs, or CRC plus other assoc. cancer, in one person, regardless of age
3. CRC that is MSI high or under age 60
4. CRC or assoc. tumor in at least 1 FDR under 50
5. CRC or assoc. tumor at any age in 2 first or second degree relatives

Front 48

What percent of sporadic tumors have MSI?
What % of HNPCC tumors have MSI?

Back 48

10-15% of sporadic tumors
95% of HNPCC tumors

Front 49

What is the American founder mutation in MSH2? (HNPCC)

Back 49

deletion of exons 1-6

Front 50

In HNPCC, what is significant about those with mutation in MSH6?

Back 50

They may have a 30% less risk for colon cancer

Front 51

Features of Fanconi Anemia

Back 51

short stature
skeletal and dev. anomalies
increased leukemia risk
increased risk of other blood and solid cancers

Front 52

Fanconi anemia assoc. with BRCA2 mutations also causes increased risk of what solid cancer?

Back 52

brain tumors

Front 53

If you see polyposis in a family and it's all in one generation, what shoud you immediately think of?

Back 53

MYH associated polyposis, which is recessive

Front 54

Homozygous mutations in what gene lead to a very severe HNPCC phenotype, but cluse low penetrance or no increased cancer risk in heterozygous form?

Back 54

PMS2

Front 55

Which HNPCC gene can be assoc. with cafe au lait spots?

Back 55

PMS2

Front 56

What percent of families that meet Amsterdam criteria have no detectable HNPCC mutation or MSI?

Back 56

up to 45%

Front 57

Features of Familial Colorectal Cancer Type X

Back 57

HNPCC-like with no identifiable mutation or MSI.
No HNPCC-associated cancers besides colon
later onset
lower chnce of 2nd tumors
due to unknown genes

Front 58

What Prior Probabliity is considered reasonable for offering BRCA testing?

Back 58

5-10%

Front 59

Best known Prior Probablity model for BRCA mutation

Back 59

Bayes Model (formerly BRCAPro)
also assess likelihood of MMR mutation and pancreatic cancer mutation

Front 60

Breast/ovarian cancer gene other than BRCA1/2

Back 60

RAD51

Front 61

Describe the basis of PARP inhibitor therapy

Back 61

PARP is an enzyme in DNA base excision repair. BRCA1/2 mutant cells still have this type of repair. Inhibiting it causes the cell to die, sparing normal cells.

Front 62

BRCA1/2 mutant cells are deficient in what type of DNA repair?

Back 62

homologous recombination DNA repair

Front 63

2 Breast cancer aromatase inhibitor trial studies

Back 63

WISE, GOSS

Front 64

Choroid plexus tumors are strongly assoc. with what cancer syndrome?

Back 64

Li-Fraumeni (p53)

Front 65

4 low penetrance breast cancer genes (new findings)

Back 65

CHK2 1100delC
PALB2
ATM
BRIP1

Front 66

Up to what percent of FAP mutations are de novo germline mutations?

Back 66

up to 30%

Front 67

Lifetime risk of colorectal cancer for a person with inflammatory bowel disease

Back 67

15-40%

Front 68

Function of normal MYH protein

Back 68

base-excision repair

Front 69

Carrier freq. for MYH mutations

Back 69

about 1%

Front 70

Onset of colon cancer for MYH

Back 70

50s

Front 71

Other cancers assoc. with MYH

Back 71

duodenal
ovarian
bladder
skin (even sebaceous gland tumors, like Lynch)

Front 72

Features of Lynch-associated colon cancer

Back 72

right sided
onset before 50
signet ring
mucinous
tumor-infiltrating lymphocytes
medullary pattern

Front 73

Cancers assoc. wtih Juvenile polyposis syndrome

Back 73

colon cancer (39%)
gastric cancer (21%)
small bowel

Front 74

Recommended mgmt for hereditary diffuse gastric cancer

Back 74

prophylactic total gastrectomy at age 20

Front 75

Most common type of renal cell carcinoma?

Back 75

clear cell (70-80%)
chromophile-papillary (10-15%)

Front 76

Key difference btwn hereditary and sporadic renal cell carcinoma

Back 76

hereditary=multifocal, bilateral, early-onset
sporadic=solitary, dx after age 60

Front 77

Name 4 syndromes assoc.w ith renal cell carcinoma

Back 77

von Hippel-Lindau
Hereditary Papillary Renal Carcinoma
Birt-Hogg-Dube
Hereditary Leiomyomatosis and Renal cell cancer

Front 78

How sensitive is genetic testing for von Hippel-Lindau?

Back 78

nearly 100%

Front 79

What % of von Hippel-Lindau is sporadic?

Back 79

20%

Front 80

Most common tumors in von Hippel-Lindau

Back 80

hemangioblastomas-benign

Front 81

Locations of hemangioblastomas in von Hippel-Lindau

Back 81

cerebellum (80%)
retina (40%)
spine (20%)

Front 82

What % of VHL patients get endolymphatic sac tumors (ears)?

Back 82

10%

Front 83

Pheochromocytoma is associated with which renal cell carcinoma syndrome? How can this affect diagnosis?

Back 83

VHL
Adrenal glands produce only noradrenaline.
Biochem analysis of adrenaline and noradrenaline can lead to diagnosis.

Front 84

Screening for VHL

Back 84

Full MRI of brain and spine at 11
Eye exam annually in childhood
MRI/CT scan for abdominal tumors
Biochem screening

Front 85

Features of hereditary papillary renal carcinoma

Back 85

bilateral, multifocal
onset usually 50-70
only affects kidney
due to activation of proto-oncogene c-MET

Front 86

Gene assoc. With Hereditary papillary renal carcinoma

Back 86

c-MET

Front 87

What syndrome is assoc. with quadriradial figures of the chromosomes? What cancer is assoc. with this syndrome?

Back 87

Fanconi pancytopenia
AMML squamous cell

Front 88

Features of Nijmegen breakage syndrome

Back 88

short stature, microcephaly, normal IQ with regression, sloping forehead, micrognathia, long nose, recurrent infections, anemia, thrombocytopenia, multiple tumor types. NBS1 gene (nibrin)

Front 89

What syndrome?
sparse colon polyps
hypopigmented macules
frontal balding
ridged and pigmented nails

Back 89

Cronkhite-Canada syndrome
colonic polyposis with alopecia and nail pigmentation, without family history or risk of malignancy

Front 90

3 regions of the chromosomes assoc. with Hereditary Dysplastic Nevus syndrome (FAMMM)

Back 90

1p
9p
12q

Front 91

What are Wermer and Sipple syndromes?

Back 91

Wermer = MEN1
Sipple =MEN2

Front 92

What is TAR syndrome?

Back 92

Thrombocytopenia, Absent radius syndrome
radial aplasia, normal thumbs
thrombocytopenia at 2 months-4 years
jaw hypoplasia
septal cardiac defects
autosomal recessive