Genetics

Question 1

PLAG1

Answer 1

Pleomorphic adenoma (benign parotid gland tumor)

Question 2

MECT1, MAML2 fusion gene

• balanced translocation of (11;19)(q21;p13)

Answer 2

Mucoepidermoid carcinoma (malignant salivary gland tumor)

Question 3

Heterozygous LOF mutation in receptor tyrosine kinase (RET)

Answer 3

Hirschsprung disease

Question 4

Mutation of p53, downregulation of CDKN2A (p16/INK4a) in early stages
- late stage: amplification of EGFR, ERBB2, MET, cyclin D1, cyclin E

Answer 4

Esophageal adenocarcinoma

Question 5

LOF mutations in p53, E-cadherin, NOTCH1

• amplification of SOX2
• overexpression of cyclin D1

Answer 5

Squamous cell carcinoma of esophagus

Question 6

LOF mutation in tumor suppressor CDH1, which encodes E-cadherin

Answer 6

Diffuse gastric adenocarcinoma

Question 7

Mutations that lead to increased signaling via the Wnt pathway:

• LOF mutation in APC (adenomatous polyposis coli)
• LOF mutation in TGFb signaling, BAX, and CDKN2A

Answer 7

Sporadic intestinal-type gastric carcinoma

Question 8

T(11;18)(q21;q21)

Less common: t(1;14)(p22;q32) and t(14;18)(q32;q21)

Answer 8

Activate NFkb -> promoting B cell growth -> MALToma

Question 9

• GOF mutation in receptor tyrosine kinase KIT or over-expression of PDGFRA

OR mutations in genes encoding mitochondrial succinate DH (SDHA, SDHB, SDHC, SDHD)

Answer 9

GI Stromal Tumor (GIST)

NOTE: KIT or PDGFRA mutations respond to tyrosine kinase inhibitor imatinib, tumors without these mutations do not

Question 10

HLA-DQ2, HLA-DQ8 alleles

Answer 10

Celiac disease