Chap 15: cancer Genetics and Genomics Flashcards
How many polyps is required for a person to have in the diagnosis of familial adenomatous polyposis?
100 or 10-100 in individual with a relative
What is the rate limiting step in FAP for adenoma formation?
somatic mutation of the wild-type APC gene
Syndrome associated with adenomatous polyps, osteomas and soft tissue tumors
Gardner syndrome
What is Turcot Syndrome?
colon cancer and CNS tumors usually medulloblastoma
Colon cancer surveillance guidelines for familial adenomatous polyposis starts at what age and continues how often?
Starts at age 10-12; colonoscopy every 1-2 years
A patient with FAP and no APC mutation should be investigated for what other mutation?
MYH mutations especially if there is a family history suggestive of AR inheritance
What are passenger mutations?
- Are not recurrent in particular cancer types
- Occur as the cancer develops, rather than directly causing the neoplasia to develop or progress
What are driver gene mutations?
- repeated in high frequency in many samples
- involved in development or progression of the cancer
Types of malignancies associated with MEN2A?
- medullary carcinoma of thyroid
- pheochromocytoma
- benign parathyroid adenomas
Tumors associated with MEN2B?
- Medullary thyroid
- Pheochromocytomas
- Benign parathyroid adenomas
- Neuromas (mucosal surface of mouth and lips and along the GI tract.
Mutation responsible for Multiple Endocrine Adenomatosis?
- RET gene
- encodes a cell-surface protien that contains an extracellular domain that can bind signaling molecules and a cytoplasmic tyrosine kinase domain.
Familial disorder/cancer associated with RB1
Familial Retinoblastoma
Familial disorder/cancer associated with VHL
von Hippel-Lindau syndrome
Familial disorder/cancer associated with MLH1, MSH2
Lynch sundrome
Familial disorder/cancer associated with TP53
Li-Fraumeni syndrome
List the chromosomal mechanisms that could lead to loss of heterozygosity for DNA markers at or near a tumor suppressor gene in an individual heterozygous for an inherited germline mutation.
- Epigenetic silencing
- Mutation
- Somatic recombination
- Loss and duplication
- Chromosomal loss
What is the general population risk for breast cancer in females?
12 %
What is the cancer risk when BRCA1 and BRCA2 mutations are present in a male?
- BRCA1: 1-2%
- BRCA2: 5-10%
- What is the underlying cause of Lynch syndrome?
- Loss of function mutations
- DNA repair genes
- MLH1, MSH2, MSH6, PMS2 (encode mismatch repair protiens)
- What are the function of the Lynch syndrome mismatch repair genes?
- Tumour supressor genes
- Repair incorrect DNA base pairing
Region of DNA most affected by lack of mismatch repair protiens? what is this phenotype called?
- Microsatellites
- Because slippage of the strand being synthesized on the template strand can occur more readily when a short tandem repeat is being synthesized
- Microsatellite instability-positive (MSI+)
Translocation and the chimeric protien associated with Chronic myelogenous leukemia (CML)
- t(9:22)(q34;q11)
- Philadelphia chromosome
- der (22) is the Philadelphia chromosome
- novel Chimeric protien is bcr-abl1
What is the function of the oncogene ABL1?
- Tyrosine kinase
Effective tyrosine kinase inhibitor used in the treatment of CML
- Imatinib (Gleevac)
Given the characteristic chromosome translocation name the human malignant neoplasm and affected proto-oncogene.
t(8;22)(q24;q11)
- Burkitt Lymphoma
- MYC
Given the characteristic chromosome translocation name the human malignant neoplasm and affected proto-oncogene.
t(8;14)(q24;q32)
- Burkitt Lymphoma
- MYC
Amplification of the MYCN proto-oncogene encoding N-Myc is an important clinical indicator in what childhood cancer?
- Neuroblastoma
Name the driver gene and tumor type treated by the following FDA approved targeted therapy:
Gefitinib: Tyrosine kinase inhibitor
- Activated EGFR
- Non-small cell lung cancer
Name the driver gene and tumor type treated by the following FDA approved targeted therapy:
Imatinib, nilotinib, dasatinib
- Chronic myelogenous leukemia and gastrointestinal stromal tumor
- Abl, KIT, PDGF
Name the driver gene and tumor type treated by the following FDA approved targeted therapy:
Trastuzumab: Anti-***monoclonal antibody
- Amplified HER2
- Breast Cancer
Name the driver gene and tumor type treated by the following FDA approved targeted therapy:
Crizotinib: Tyrosine kinase inhibitor
- translocated ALK
- Non-small cell lung cancer
Name the driver gene and tumor type treated by the following FDA approved targeted therapy:
Trametinib: Serine-threonine kinase inhibitor
- Activated MEK
- Melanoma
Name the driver gene and tumor type treated by the following FDA approved targeted therapy:
Vemurafenib: Serine-threonine kinase inhibitor
- Activated BRAF kinase
- Melanoma
