Cancer

Question 1

3 types of cancer (family assessment)

Answer 1

1. sporadic (60%) 2. familial (30%) 3. hereditary (10%)

Question 2

BRCA1/2 associated cancers (5)

Answer 2

breast (male & female) ovary prostate pancreatic melanoma

Question 3

CDH1 associated cancers

Answer 3

breast (lobular) diffuse gastric cancer (most likely to metastasize to nearby tissues or bones) prostate colon & rectum Somatic mutations associated with : endometrial, ovarian, and prostate

Question 4

HNPCC (Lynch syndrome) associated cancers (8)

Answer 4

colorectal uterine ovarian stomach gall bladder urinary tract small bowel brain/CNS

Question 5

PTEN associated cancers (5) & other findings

Answer 5

breast kidney thyroid uterine colon other findings: hamartomatous overgrowth & skin lesions

Question 6

Bannayan-Riley-Ruvalcaba syndrome

Answer 6

PTEN mutation clinical features: -macrocephaly -hamartomatous intestinal polyps -lipomas -hemangiomas -pigmented penile macules -DD -large birth weight -joint hyperextensibility -myopathic process in proximal muscles -Hoshimoto’s thyroiditis -multinodular goiter -thyroid adenoma non-medullary thyroid cancer

Question 7

Proteus syndrome

Answer 7

PTEN mutation -ovarian cystadenomas, testicular tumors, menangiomas, monomorphic adenomas of parotid gland -hamartomatous tissue overgrowth -congenital malformation -hyperostosis (excessive growth of bone) -epidermal and connective tissue nevi which occur in a mosaic pattern

Question 8

Lhermitte-Duclos disease

Answer 8

dysplastic gangliocytoma of the cerebellum adult onset occurs in patients with germline PTEN mutations (Tumor of the cerebellum)

Question 9

STK11 associated cancers (8)

Answer 9

small intestine stomach pancreas colon esophagus breast lung ovary

Question 10

Peutz-Jeghers syndrome

Answer 10

STK11 mutation hamartomatous polyps of the GI tract (small intestine, colon, stomach & rectum) mucocutaneous pigmentation

Question 11

TP53 associated cancers (5)

Answer 11

sarcoma adrenocortical carcinoma breast leukemia brain tumors

Question 12

Li-Fraumeni

Answer 12

TP53 mutation AD CHEK2 gene mutation (sometimes) childhood/young adult onset

Question 13

ATM associated cancers (6)

Answer 13

breast stomach bladder pancreas lung ovary

Question 14

ataxia-telangiectasia

Answer 14

ATM homozygous mutation hypersensitive to radiation

Question 15

PALB2 associated cancers (2)

Answer 15

breast (male & female) ovary

Question 16

Fanconi anemia

Answer 16

BRCA2, BRIP1, PALB2 and FANC genes homozygous -congenital malformations of the heart, renal system, and limbs -dermal pigmentary changes -predisposition to development of malignancies -progressive bone marrow failure resulting in anemia, leukopenia, and thrombopenia -hypersensitivity to DNA crosslinking agents

Question 17

CHEK2 associated cancers (9)

Answer 17

breast prostate lung colon kidney thyroid ovary brain tumors osteosarcoma

Question 18

Cowden syndrome associated cancers, gene, & features

Answer 18

PTEN mutation breast, kidney, thyroid (follicular), uterine & colon cancers associated features: -enlarged head -acral keratoses -oral papilomas -lipoma -colon polyps -thyroid nodules

Question 19

Lynch syndrome (HNPCC) associated genes

Answer 19

MLH1, MSH2, MSH6, PMS2, EPCAM

Question 20

Familial Adenomatous Polyposis associated gene & features

Answer 20

APC gene mutation features: -CHRPE epidermoid cysts supernumerary teeth duodenal polyposis >100 colorectal adenomatous polyps

Question 21

FAP associated cancers

Answer 21

colorectal other associated cancers: thyroid brain hepatoblastoma osteoma desmoid tumor adrenal gland adenoma duodenal adenoma

Question 22

Attenuated FAP (AFAP) associated gene, cancers & features

Answer 22

APC gene colorectal cancer 3-99 adenomas

Question 23

MUTYH adenomatous polyposis associated gene & features

Answer 23

MUTYH gene features: CHRPE 20-100 colorectal adenomatous polyps Autosomal recessive

Question 24

MUTYH adenomatous polyposis associated cancers

Answer 24

Colorectal other cancers: duodenal osteomas ovary bladder skin breast

Question 25

Juvenile polyposis syndrome associated genes & features

Answer 25

SMAD4 & BMPR1A genes other features: >3-5 juvenile polyps in colorectum or GI tract

SMAD4 also involved in HHT

Question 26

Juvenile polyposis syndrome associated cancers

Answer 26

colorectal other cancers: stomach small intestine pancreas

Question 27

Hyperplastic polyposis syndrome associated genes, cancer & features

Answer 27

KRAS & BRAF genes colorectal cancer features: large, right-sided polyps (KRAS) many small, left-sided polyps (BRAF)

These genes are also involved in Noonan syndrome

Question 28

Hereditary mixed polyposis syndrome associated genes, cancer & features

Answer 28

SCG5 & GREM1 genes colorectal cancer other features: mixed histology polyps including hyperplastic, adenomatous, and juvenile polyps