Heritable Cancerous Conditions

Question 1

MEN 1: gene, tumors

Answer 1

AD; MEN1 tumor suppressor LOF; pancreatic tumors (mostly gastrinoma), pituitary adenoma and parathyroid hyperplasia … (some lipomas)

Question 2

MEN2A: gene, tumors

Answer 2

AD; RET proto-oncogene GOF; parathyroid hyperplasia, medullary thyroid cancer, pheochromocytoma

Question 3

MEN2B: gene, tumors

Answer 3

AD; RET gene proto-oncogene GOF; medullary thyroid cancer; pheochromocytoma, marfanoid habitus, mucosal neuromas

Question 4

Ataxia-telangiectasia: gene, syndrome

Answer 4

AR inheritance; ATM gene for DS break (ionizing radiation; x or gamma ray) repair; cerebellar atrophy w/ ataxia, oculocutaneous telangiectasia, immunodeficiency with sinopulmonary infections, increased cancer risk

Question 5

Xeroderma Pigmentosum: gene, syndrome

Answer 5

AR inheritance; XPA gene for T dimerization nucleotide excision repair due to sun damage; premature skin aging and increased melanoma / SCC risk

Question 6

Fanconi anemia: gene, syndrome

Answer 6

AR inheritance; many genes involved in homologous recombination to repair cross-linking; causes marrow failure, AML, solid tumors and developmental issues

Question 7

Bloom syndrome: gene, syndrome

Answer 7

AR; mutations of BLM gene for DNA helicase > genomic instability via excessive crossover and sister chromatid exchanges; short stature, facial rash, narrow face, small jaw, big ears/nose, pigmentation issues, cafe au lait, telangiectasia; immune deficiency; predisposes to various cancers

Question 8

HNPCC / Lynch syndrome; gene, syndrome

Answer 8

AD, mutations in MSH2, MLH1, MSH6 or PMS2 genes for mismatch repair

colon / endometrial carcinoma; GI adenomas; ovarian cystadenocarcinoma

(50-80% colon cancer risk)

Question 9

Familial adenomatous polyposis; gene, tumors

Answer 9

AD; APC tumor suppressor (normally breaks down beta-catenin; high beta-catenin > transcriptional activation)

colorectal polyps/cancer (some gastric/duodenal)
desmoids + osteomas
brain tumors
thyroid tumors

(100% colon cancer risk)

Question 10

Von Hippel-Lindau syndrome; gene, tumors

Answer 10

AD; VHL tumor suppressor

cerebellar hemangioblastomas, retinal hemangiomas

congenital CYSTS / TUMORS in KIDNEY, LIVER, PANCREAS

increased risk of CLEAR CELL RENAL CARCINOMA (maybe bilateral) and PHEOCHROMOCYTOMA

Question 11

Li Fraumeni Syndrome; gene, tumors

Answer 11

AD; P53 tumor suppressor; sarcoma, breast cancer, brain tumors, adrenocortical adenoma, leukemia

Question 12

Tuberous Sclerosis: inheritance + tumors

hints:
renal, cns, skin, heart … what kinds of tumors in each
and what non-tumorous lesions?

Answer 12

AD inheritance

kidney, liver, pancreas cysts

renal ANGIOMYOLIPOMA

BRAIN cortical tubers + subependymal HAMARTOMA

ASH-LEAF skin patches + cutaneous facial ANGIOFIBROMA

cardiac RHABDOMYOMA

Question 13

NF1: inheritance + tumors

Answer 13

AD; neurofibromas, optic gliomas, Lisch nodules (pigmented iris lesion) and CAL spots (bilateral, smaller, assoc. with axillary/inguinal freckling)

Question 14

NF2: inheritance + tumors

Answer 14

AD; bilateral acoustic neuromas; (multiple meningiomas, gliomas, SC ependymomas)

Question 15

Peutz-Jeghers syndrome

mutation, tumors, colon cancer risk

Answer 15

STK11 mutation

colon cancer
upper GI cancer
pancreatic
breast

(40% colon cancer risk)

Question 16

On what chromosome is VHL found?

Answer 16

Chromosome 3, small arm (3p)

deletion/inactivation causes:

Hemangioblastoma (cerebellar)
Renal carcinoma (clear cell)
Pheochromocytoma

(von Hippel got the HRP from unprotected sex…)

Question 17

What is the function of VHL gene?

consequence for treatment?

Answer 17

normally INHIBITS HYPOXIA INDUCIBLE FACTORS such as…

VEGF
PDGF

tx with ANGIOGENESIS INHIBITORS is useful

Question 18

on which chromosome is NF-1?

Answer 18

17

Question 19

on which chromosome is Rb?

tumors?

Answer 19

13

retinoblastoma
osteosarcoma

Question 20

on which chromosome is WT-1?

Answer 20

11

Question 21

What are the facial angiofibromas like in tuberous sclerosis? (derma description)

Answer 21

pink-yellow papules in butterfly distribution over nose, cheeks + nasolabial folds

Question 22

Tuberous sclerosis: cardiac tumor type and functional consequences of it

Answer 22

cardiac rhabdomyoma

LV hypertrophy with narrow outflow tract due to SEPTAL MASS

creates a systolic ejection murmur

Question 23

What is Gardner syndrome?

Hint: related to another familial cancer syndrome but with extra features

Answer 23

Familial Adenomatous Polyposis, plus…

1. Bone + soft tissue tumors
2. Retinal pigment epith. hypertrophy
3. Teeth are impacted/supernumerary

(think Gaucher = sphingolipidosis w/ bone issues > Gardner = FAP w/ bone issues)

Question 24

What is Turcot syndrome?

Hint: related to other familial cancer syndromea but with extra features

Answer 24

FAP / HNPCC, plus…

Malignant CNS tumors - medulloblastoma, glioma

(think TURcot = TURban = head tumors)