Genetics

Question 1

What is the Knudson hypothesis?

Answer 1

concept of “two-hit” genetic mutations causing cancer, with one “hit” occurring because of inherited mutation and second one occurring sporadically, later Ex: Retinoblastoma

Question 2

List oncogenes in cancer genomics (2)

Answer 2

MET - renal
RET - endocrine tumors

Question 3

List the genetic concept behind the Vogelstein model

Answer 3

Tumorogenesis: how something moves from non-cancer to cancer. Acquired mutations over time lead to deregulation of cells and cancer development

Question 4

Review the genetic test report/nomenclature addressed in final clinical case scenario of review

Answer 4

Do it

Question 5

Week 3 quiz questions

Answer 5

review

Question 6

Management of “variant favor polymorphism”

Answer 6

Aka Benign or likely benign (mutational finding, vs pathogenic/VUS/etc)

Question 7

Differentiate between use of Claus vs Gail vs Tyrer-Cusick vs Canrisk

Answer 7

When one or the other is better

Question 8

Features of CMMRD

Question 9

Amsterdam vs Bethesda criteria

Question 10

CRC genes picture

Answer 10

Question 11

Syndromes causing pancreatic adenocarcinoma vs PNETs

Answer 11

Adeno - BRCA, CDKN2A
PNET - MEN (endocrine syndromes)

Question 12

Amsterdam criteria

Answer 12

Revised version (Amsterdam 2) - Lynch cancers (CRC, endometrial, bladder, small bowel, renal pelvis)

USE: Clinical testing to check if genetic testing for Lynch should be done (historic)

3-2-1-1-0 rule
3 relatives with cancer
2 successive generations
1 first degree relative of the other two
one diagnosis <50 y/o
Exclude FAP

Question 13

Bethesda criteria (why and what they are)

Answer 13

Why: Warrants testing for Lynch in CRC by MSI or IHC

• CRC <50 y/o
• CRC w/ MSI-H in age <60
• Synchronous or metachronous LS tumors regardless of age
• CRC in pt with >1 1st degree relative with LS cancer at age <50
• CRC in pt with >2 1st degree relatives with LS cancer at any age

Question 14

week 8 quiz questoins

Answer 14

review

Question 15

Describe PTEN/Cowden

Question 16

Describe Gorlin syndrome

Answer 16

Nevoid basal cell carcinoma

Question 17

Describe NF1

Question 18

review week 9 module

Answer 18

do it

Question 19

Autosomal recessive condition causing melanoma - noted in week 9 module

Question 20

Review pharmacogenomics lecture (week 9 #3). Know the most common type of pathogenic variant is associated with different clinical applications (CNV, InDels, SNPs?)

Question 21

Syndromes associated with pancreatic NETs

Question 22

Syndromes associated with pancreatic adenocarcinomas

Answer 22

BRCA syndromes

Question 23

Li fraumeni syndrome

Question 24

Von Hipple Lindau syndrome

Answer 24

key features, risk factors, pathology (clear cell)

pancreatic NET
pheo
hemangioblastomas
RCC

Question 25

Genes associated w/ hematologic malignancies

Question 26

NCCN guidelines for hereditary melanoma syndrome testing

Question 27

week 10 endocrine

Answer 27

review

Question 28

MEN1

Answer 28

HyperCa, parathyroid tumors, pituitary adenoma, gastrinoma

Question 29

MEN2

Answer 29

Associated with RET mutation protooncogene Pheochromocytoma Medullary thyroid carcinoma

Question 30

Familial medullary thyroid cancer

Answer 30

***

Question 31

Hereditary paraganglioma syndromes

Answer 31

SDHB - AD hereditary paraganglioma-pheochromocytoma syndrome, GIST, renal cancer, AR mitochondrial complex II deficiency; highest chance for malignant transformation of paraganglioma

Question 32

SHDA review

Answer 32

distinctions between affected and unaffected families in the consensus UK guidelines (reduced penetrance gene)

Question 33

Kidney cancer assoc w/ Burt Hogg Dube

Answer 33

chromophobe oncocytoma

Question 34

week 11 quiz review attention

Question 35

Which SDHX gene is maternally imprinted?

Answer 35

SDHD Must be inherited from father for pathogenicity

Question 36

Which oncogene is associated with hereditary kidney cancer?

Answer 36

MET - hereditary papillary renal carcinoma