TABLE 1.
Genea | Gene/protein function | Phenotype | Histopathologic features or most common histopathologic subtype of melanoma |
---|---|---|---|
Cyclin dependent kinase inhibitor 2A (CDKN2A) | • Tumor suppressor • Two main alternate transcripts: (a) p16 inhibits CDK4 and phosphorylation of RB; (b) p14ARF inhibits HDM2 and ubiquitination of p53 |
• Melanocytic nevi, melanoma, pancreatic, upper GI, and respiratory cancers; astrocytoma, neurofibromas and schwannomas (mutation affecting p14ARF) | • Superficial spreading melanoma • Pigmentation, pagetoid scatter, and spindle cell morphology in vertical growth phase |
Cyclin dependent kinase 4 (CDK4) | • Oncogene • Inhibits binding of p16 tumor suppressor leading to phosphorylation of RB and cell cycle progression |
• Melanocytic nevi, melanoma, pancreatic cancer | • Superficial spreading melanoma • Pigmentation and pagetoid scatter |
Telomerase reverse transcriptase (TERT) | • Telomerase reverse transcriptase, a component of telomerase • Normally repressed in postnatal somatic cells leading to shortening of telomeres |
• Melanoma, melanocytic nevi, other reported cancers (ovarian, renal cell, bladder, breast, and bronchial cancer) | • Nodular and superficial spreading melanoma |
Protection of telomeres 1 (POT1) | • Constituent of shelterin complex that regulates telomere processing and stability | • Melanoma, other reported cancers (glioma, chronic lymphocytic leukemia, colorectal, breast, and lung cancers) | • Superficial spreading melanoma |
ACD shelterin complex subunit and telomerase recruitment factor (ACD) | • Constituent of shelterin complex that regulates telomere processing and stability | • Melanoma, other reported cancers (breast, ovarian, cervical, uterine, thyroid, colon, lung, renal, urinary, prostate and esophageal cancers, lymphomas and leukemias) | • Superficial spreading melanoma, and lentigo maligna melanoma |
TERF2 interacting protein (TERF2IP) | • Constituent of shelterin complex that regulates telomere processing and stability | • Melanoma, other reported cancers (breast, ovarian, cervical, uterine, thyroid, colon, lung, renal, urinary, prostate and esophageal cancers, lymphomas and leukemias) | • Superficial spreading melanoma, and lentigo maligna melanoma |
Melanocyte inducing transcription factor (MITF) | • A melanocytic lineage-specific transcription factor, regulating differentiation, proliferation and survival of melanocytes | • Melanoma, renal cell carcinoma • Darker hair, fair skin, and non-blue eye color |
• Amelanotic • Thicker tumors (in some populations) • Nodular melanoma |
Melanocortin-1 receptor (MC1R) | • G protein coupled receptor for melanocyte-stimulating hormone • Controls melanogenesis and thus skin and hair color |
• Melanoma • Red hair, freckling, light skin, and UV sensitivity (loss-of-function variants) |
• Anatomic site (arms; in carriers of more than one high-risk variant) |
BRCA1 associated protein 1 (BAP1) | • Deubiquitinating enzyme, BRCA1 binding partner • Implicated in chromatin modulation, transcriptional regulation, and DNA damage repair |
• BAP1-inactivated nevi, uveal melanoma, cutaneous melanoma, mesothelioma, and renal cell carcinoma • Other reported tumors (basal cell carcinoma, meningioma, cholangiocarcinoma, breast, lung, pancreatic, and thyroid cancer) |
BAP1-inactivated nevi: • Exclusively or predominantly intradermal • Associated common nevus component often present (a combined nevus) • Epithelioid melanocytes with round to oval vesicular nuclei and abundant amphophilic cytoplasm • May show smaller epithelioid cells without abundant eosinophilic cytoplasm • May show rhabdoid features |
Gene symbols and nomenclature obtained from the HUGO Gene Nomenclature Committee.