Oncology

Question 1

p53 - associated cancers

Answer 1

Tumor suppressor gene - loss of function results in an increased risk of cancer

Common to many cancers, Li-Fraumeni syndrome

Question 2

APC - associated cancers

Answer 2

Tumor suppressor gene - loss of function results in an increased risk of cancer

Adenomatous Polyposis Coli

Colorectal cancer

Question 3

BRAC 1 - associated cancer

Answer 3

Breast and ovarian cancer

Tumor suppressor gene - loss of function results in an increased risk of cancer

Question 4

BRAC 2 - associated cancer

Answer 4

Breast and Ovarian

Tumor suppressor gene - loss of function results in an increased risk of cancer

Question 5

NF1 - associated cancer

Answer 5

Neurofibromatosis

Tumor suppressor gene - loss of function results in an increased risk of cancer

Question 6

Rb gene - associated cancer

Answer 6

Rb = retinoblastoma

Tumor suppressor gene - loss of function results in an increased risk of cancer

Question 7

WT1 gene - associated cancer

Answer 7

Wilm’s Tumor
- nephroblastoma; most common kidney cancer in children

Tumor suppressor gene - loss of function results in an increased risk of cancer

Question 8

RET - associated cancer

Answer 8

MEN 2

Question 9

PABL2 - associated cancer

Answer 9

Breast cancer

Partner and localiser of the BRAC2 gene

Question 10

PTEN - associated cancer

Answer 10

Cowden syndrome - growth of multiple hamartomas and increased risk of breast, thyroid and endometrial cancer

Question 11

3 targetable mutations in NSLC?

Answer 11

EGFR
ALK
ROS

Question 12

EGFR mutation in NSCLC

Answer 12

Classic phenotype - young, female, Asian, never smoked
Next generation sequencing (NGS) on tumour sample
Treat with Tyrosine Kinase Inhibitors: Afatinib

Question 13

Mechanisms of resistance to TKI in NSCLC

Answer 13

EGFR T790M mutation - Rx with Osimertinib

HER 2 amplification
MET amplification
Small-cell transformation

Question 14

NSCLC and ALK rearrangements

Answer 14

Anaolastic lymphoma kinase (ALK)
ALK rearrangements in 5% of NSCLC
Non smokers: EGFR and KRAS wild-type
Detected by FISH

Treat with TKI: crizotinib, ceritinib, alectinib
Alectinib most efficacious and best CNS penetrance

Question 15

Rare moderate breast cancer risk alleles

Answer 15

ATM
FANC C
FANC M
BLM
PALB2
CHEK2
BRIP1

Question 16

Polyp associated colorectal cancer risk

Answer 16

FAP - APC gene mutation (chromosome 5q)
MutYH - phenotypically similar to FAP
Peutz -Jeghers Syndrome (STK11)
HPS

Question 17

Non polyp associated colorectal cancer risk

Answer 17

Lynch syndrome: MLH1 MSH2, MSH6, PMS2

Familial CRC Syndrome X

Question 18

Peutz -Jegher Syndrome

Answer 18

STK11 gene (autosomal dominant)
Hamartomatous polyposis
Kip, buccal, palm pigmentation
Small intestine - intrasusseption in kids
Increased risk CRC and breast cancer

Question 19

Lynch syndrome

Answer 19

Hereditary non-polyposis colorectal cancer
Germaine mutation in DNA mismatch repair gene
Autosomal dominant
CRC, endometrial, ovarian

First: test tumor for evidence of DNA MMR defect
- microsatellite instability testing using PCR
- immunohistochemistry staining 4 MMR proteins
Second: Germaine testing for MMR gene mutation