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37 Cards in this Set
- Front
- Back
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What is the sequence of mutations in colon cancer?
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1. Loss of APC causes hyper-proliferative epi/early adenoma
2. Activation of K-ras causes an intermediate adenoma 3. Loss of 18q causes a late adenoma 4. Loss of TP53 causes a carcinoma Other losses cause metastasis |
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What genetic abnormality is associated with the transition of an adenoma to a carcinoma?
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p53
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What are the two broad mutation-based classifications of CRC?
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Non-hypermutated: 58 gene mutations/tumor
Hypermutated: 728 mutations/tumor |
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What are the different kinds of proteins that are mutated in CRC?
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Cell adhesion
Signal transduction Transcriptional regulation Transport Cellular metabolism Intracellular trafficing RNA metabolism Other |
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What occurs in WNT signalling?
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1. WNT Ligand binds to receptor
2. APC, GSK3, Axin dissociates 3. Beta-catenin isn't broken down anymore 4. Beta-catenin goes to the nucleus and transduces signals. |
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How is WNT signalling altered in CRC?
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APC mutations cause constituitive beta catenin signal transduction-->hyper-proliferative epithelium
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What are the molecular classifications of CRC?
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Chromosomal instability (60%)
DNA misatch repair (3-5%) CpG-island methylator phenotype (30%) |
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What is the mechanism of cancer in chromosmal instability CRC?
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Somatic alterations in tumor suppressor genes p53, APC, SMAD4
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What is the precursor lesion to chromosomal instability CRC?
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Adenomas
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What are the genomic characteristics of chromosomal instability CRC?
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Copy number variation
Loss of heterogosity Non-hypermutated. |
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What is the mechanism of the DNA mismatch repair CRC?
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Germline gene mutations in DNA mismatch repair genes
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What genes are mutated in DNA mismatch repair CRC?
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MLH1
MSH2 MSH6 PMS2 |
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What are the genomic characteristics of DNA mismatch repair CRC?
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Microsatellite instability
Hypermutation |
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What's the precursor lesion for DNA mismatch repairs?
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Adenomas
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What are the precursor lesions for CpG-island methylator phenotype?
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sessile serrated polyp/adenoma
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What is the course for the DNA mismatch repair cancers?
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Fast!
Develop in less than 3 years |
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What is the mechanism of CpG-island methylator phenotype CRC?
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Transcriptional inactivation of the tumor suppressor genes
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What are the implication of a KRAS mutation in colon cancer?
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You can't use cetuximab to inactivate the EGFR pathway, as it's already constituitively activated.
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What is the most common kind of colon cancer?
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Sporadic: 65-85%
Familial: 10-30% Lynch Syndrome/HNPCC: 5% |
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What's the general risk for colon cancer?
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6%
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If you have IBD, what's your cancer risk?
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15-40%
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What mutation is present in FAP?
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Protein truncating mutations in APC on 5q
30% are de novo |
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When do people with FAP get cancer?
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20.
TAKE IT OUT! SURGERY FTW!!!!!!!!!!!!!!!! YES!!!!!!!!!!!!!!! |
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What are the extra-GI findings in FAP?
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Desmoid tumors
Osteomas Supernumeray teeth Congenital hypertrophy of the retinal pigment epithelium |
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What's the characteristic ocular finding in FAP?
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Congenital hypertrophy of the retinal pigment epithelium
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What are the different types of FAP?
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Attenuated
Classic CHRPE |
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What are the characteristics of attenuated FAP?
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10-100 colonic adenomas
Older onset |
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Where is the APC gene mutated in attenuated FAP?
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5', 3' ends of the gene
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What is the inheritance of lynch syndrome?
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Autosomal dominance
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What are the clinical features of lynch syndrome?
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Early diagnosis of Lynch syndrome
FAST-GROWING CANCERS! <3 years Extracolonic cancers: endometrium, stomach, biliary tract |
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What are the Amsterdam criteria for Lynch syndrome?
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3 or more relatives with verified CRC in the family
2 or more generations 1 CRC by age 50 |
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What is microsatellite instability?
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When you have little repeats that have different sizes in different cells
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When should you start colonoscopies in people with Lynch syndrome? How often should you repeat?
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25
Every year. |
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What's the inheritance of the MYH gene?
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Autosomal recessive
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What does MYH look like?
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Like FAP!
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What process goes wrong in MYH?
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Base excision repair!
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What is the effecacy of chemo for MSI-H tumors?
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Less effective!
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