Pathology - Neoplasia Genes and Mutations

Flashcards covering key genes and mutations involved in neoplasia, including proto-oncogenes, oncogenes, and tumor suppressor genes.

Gain of function mutation

Converts proto-oncogene (normal gene) to oncogene, increasing cancer risk. Requires damage to only one allele of a proto-oncogene.

ALK

Receptor tyrosine kinase associated with Lung adenocarcinoma

EGFR (ERBB1)

Receptor tyrosine kinase associated with Lung adenocarcinoma

HER2 (ERBB2)

Receptor tyrosine kinase associated with Breast and gastric carcinomas

RET

Receptor Tyrosine kinase associated with MEN2A and 2B, medullary and papillary thyroid carcinoma, pheochromocytoma

BCR-ABL

Non-receptor tyrosine kinase associated with CML, ALL

JAK2

Non-receptor tyrosine kinase associated with Myeloproliferative neoplasms

BRAF

Serine/threonine kinase associated with Melanoma, non-Hodgkin lymphoma, colorectal carcinoma, papillary thyroid carcinoma, hairy cell leukemia

c-KIT

CytoKIne receptor (CD117) associated with Gastrointestinal stromal tumor (GIST), mastocytosis

MYCC (c-myc)

Transcription factor associated with Burkitt lymphoma

MYCN (N-myc)

Transcription factor associated with Neuroblastoma

KRAS

RAS GTPase associated with Colorectal, lung, pancreatic cancers

BCL-2

Antiapoptotic molecule (inhibits apoptosis) associated with Follicular and diffuse large B-Cell Lymphomas

Loss of function

Increases cancer risk; both (two) alleles of a tumor suppressor gene must be lost for expression of disease (the Knudson 2-hit hypothesis).

APC

Negative regulator of β-catenin/WNT pathway associated with Colorectal cancer (associated with FAP)

BRCA1/BRCA2

Associated with BReast, ovarian, prostate, pancreatic CAncers

CDKN2A

p16, blocks G1 S phase; associated with Many cancers (eg, melanoma, lung, pancreatic)

DCC

DCC—Deleted in Colorectal Cancer associated with Colorectal cancer

SMAD4 (DPC4)

DPC—Deleted in Pancreatic Cancer associated with Pancreatic cancer, colorectal cancer

MEN1

Associated with Multiple Endocrine Neoplasia type 1

NF1

Neurofibromin (Ras GTPase activating protein) associated with NeuroFibromatosis type 1

NF2

Merlin (schwannomin) protein associated with NeuroFibromatosis type 2

PTEN

Negative regulator of PI3k/AKT pathway associated with Prostate, breasT, and ENdometrial cancers

RB1

Inhibits E2F; blocks G1 S phase associated with Retinoblastoma, osteosarcoma (Bone cancer)

TP53

p53, activates p21, blocks G1 S phase associated with Most cancers, Li-Fraumeni (SBLA) syndrome (multiple malignancies at early age; Sarcoma, Breast/Brain, Lung/Leukemia, Adrenal gland)

TSC1

Hamartin protein associated with Tuberous sclerosis

TSC2

Tuberin (“2berin”) associated with Tuberous sclerosis

VHL

Inhibits hypoxia-inducible factor 1a associated with von Hippel-Lindau disease

WT1

Urogenital development transcription factor associated with Wilms Tumor (nephroblastoma)