Chap 15: cancer Genetics and Genomics

Question 1

How many polyps is required for a person to have in the diagnosis of familial adenomatous polyposis?

Answer 1

100 or 10-100 in individual with a relative

Question 2

What is the rate limiting step in FAP for adenoma formation?

Answer 2

somatic mutation of the wild-type APC gene

Question 3

Syndrome associated with adenomatous polyps, osteomas and soft tissue tumors

Answer 3

Gardner syndrome

Question 4

What is Turcot Syndrome?

Answer 4

colon cancer and CNS tumors usually medulloblastoma

Question 5

Colon cancer surveillance guidelines for familial adenomatous polyposis starts at what age and continues how often?

Answer 5

Starts at age 10-12; colonoscopy every 1-2 years

Question 6

A patient with FAP and no APC mutation should be investigated for what other mutation?

Answer 6

MYH mutations especially if there is a family history suggestive of AR inheritance

Question 7

What are passenger mutations?

Answer 7

• Are not recurrent in particular cancer types
• Occur as the cancer develops, rather than directly causing the neoplasia to develop or progress

Question 8

What are driver gene mutations?

Answer 8

• repeated in high frequency in many samples
• involved in development or progression of the cancer

Question 9

Types of malignancies associated with MEN2A?

Answer 9

• medullary carcinoma of thyroid
• pheochromocytoma
• benign parathyroid adenomas

Question 10

Tumors associated with MEN2B?

Answer 10

• Medullary thyroid
• Pheochromocytomas
• Benign parathyroid adenomas
• Neuromas (mucosal surface of mouth and lips and along the GI tract.

Question 11

Mutation responsible for Multiple Endocrine Adenomatosis?

Answer 11

• RET gene
• encodes a cell-surface protien that contains an extracellular domain that can bind signaling molecules and a cytoplasmic tyrosine kinase domain.

Question 12

Familial disorder/cancer associated with RB1

Answer 12

Familial Retinoblastoma

Question 13

Familial disorder/cancer associated with VHL

Answer 13

von Hippel-Lindau syndrome

Question 14

Familial disorder/cancer associated with MLH1, MSH2

Answer 14

Lynch sundrome

Question 15

Familial disorder/cancer associated with TP53

Answer 15

Li-Fraumeni syndrome

Question 16

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.

Answer 16

• Epigenetic silencing
• Mutation
• Somatic recombination
• Loss and duplication
• Chromosomal loss

Question 17

What is the general population risk for breast cancer in females?

Answer 17

12 %

Question 18

What is the cancer risk when BRCA1 and BRCA2 mutations are present in a male?

Answer 18

• BRCA1: 1-2%
• BRCA2: 5-10%

Question 19

• What is the underlying cause of Lynch syndrome?

Answer 19

• Loss of function mutations
• DNA repair genes
• MLH1, MSH2, MSH6, PMS2 (encode mismatch repair protiens)

Question 20

• What are the function of the Lynch syndrome mismatch repair genes?

Answer 20

• Tumour supressor genes
• Repair incorrect DNA base pairing

Question 21

Region of DNA most affected by lack of mismatch repair protiens? what is this phenotype called?

Answer 21

• 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+)

Question 22

Translocation and the chimeric protien associated with Chronic myelogenous leukemia (CML)

Answer 22

• t(9:22)(q34;q11)
• Philadelphia chromosome
• der (22) is the Philadelphia chromosome
• novel Chimeric protien is bcr-abl1

Question 23

What is the function of the oncogene ABL1?

Answer 23

• Tyrosine kinase

Question 24

Effective tyrosine kinase inhibitor used in the treatment of CML

Answer 24

• Imatinib (Gleevac)

Question 25

Given the characteristic chromosome translocation name the human malignant neoplasm and affected proto-oncogene.

t(8;22)(q24;q11)

Answer 25

• Burkitt Lymphoma
• MYC

Question 26

Given the characteristic chromosome translocation name the human malignant neoplasm and affected proto-oncogene.

t(8;14)(q24;q32)

Answer 26

• Burkitt Lymphoma
• MYC

Question 27

Amplification of the MYCN proto-oncogene encoding N-Myc is an important clinical indicator in what childhood cancer?

Answer 27

• Neuroblastoma

Question 28

Name the driver gene and tumor type treated by the following FDA approved targeted therapy:

Gefitinib: Tyrosine kinase inhibitor

Answer 28

• Activated EGFR
• Non-small cell lung cancer

Question 29

Name the driver gene and tumor type treated by the following FDA approved targeted therapy:

Imatinib, nilotinib, dasatinib

Answer 29

• Chronic myelogenous leukemia and gastrointestinal stromal tumor
• Abl, KIT, PDGF

Question 30

Name the driver gene and tumor type treated by the following FDA approved targeted therapy:

Trastuzumab: Anti-***monoclonal antibody

Answer 30

• Amplified HER2
• Breast Cancer

Question 31

Name the driver gene and tumor type treated by the following FDA approved targeted therapy:

Crizotinib: Tyrosine kinase inhibitor

Answer 31

• translocated ALK
• Non-small cell lung cancer

Question 32

Name the driver gene and tumor type treated by the following FDA approved targeted therapy:

Trametinib: Serine-threonine kinase inhibitor

Answer 32

• Activated MEK
• Melanoma

Question 33

Name the driver gene and tumor type treated by the following FDA approved targeted therapy:

Vemurafenib: Serine-threonine kinase inhibitor

Answer 33

• Activated BRAF kinase
• Melanoma