TABLE 2.
Melanoma-subordinate syndromes. The genes of melanoma-subordinate syndromes are summarized here, alongside the clinical phenotype or tumor spectrum90–96
| Gene | Syndrome | Phenotype and tumor spectrum |
|---|---|---|
| Phosphatase and tensin homolog (PTEN) | Cowden syndrome | • Mucocutaneous findings: trichilemmomas, acral keratoses, and oral papillomas sometimes with cobblestone appearance • Thyroid abnormalities (multinodular goiter, thyroiditis, and adenomas) • Macrocephaly • Breast cancer (most common malignancy) • Thyroid cancer • Genitourinary cancers (endometrial cancer and renal cell cancer) • GI tumors, including polyps and colorectal cancer • Neurologic tumors • Vascular tumors • Melanoma |
| Tumor protein p53 (TP53) | Li-Fraumeni syndrome | • Multiple cancers, lifetime risk of cancer 70% to 100% • Sarcomas (all types of soft tissue and bone sarcomas, including but not limited to osteosarcoma and rhabdomyosarcoma), except for Ewing sarcoma • Breast cancer • Brain tumors, including high-grade gliomas and medulloblastoma • Adrenocortical carcinoma • Melanoma |
| BRCA1 DNA repair associated (BRCA1), BRCA2 DNA repair associated (BRCA2) | Hereditary breast and ovarian cancer | • Breast and ovarian cancer • Other gynecologic cancers (Fallopian tubal, peritoneal, endometrial, and uterine papillary serous) • Pancreatic cancer • Prostate cancer • Colorectal cancer • Stomach and biliary cancer • Melanoma, including uveal melanoma (mainly BRCA2 mutation carriers) |
| RB transcriptional corepressor 1 (RB1) | Hereditary retinoblastoma | • Retinoblastoma, typically under the age of three •Pineoblastoma • Osteosarcoma • Soft tissue sarcomas • Melanoma |
| mutL homolog 1 (MLH1) mutS homolog 2 (MSH2) Epithelial cell adhesion molecule (EPCAM) mutS homolog 6 (MSH6) PMS1 homolog 2, mismatch repair system component (PMS2) |
Hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) | • Colorectal cancer • Endometrial cancer • Cancer of small intestine • Other genitourinary cancers (ureteral, uterine, and renal pelvis) • Melanoma |
| Damage specific DNA binding protein 2 (DDB2) ERCC excision repair 1, endonuclease non-catalytic subunit (ERCC1) ERCC excision repair 2, TFIIH core complex helicase subunit (ERCC2) |
Xeroderma pigmentosum | • Extreme sensitivity to UV light • Freckling (solar lentigines) in early childhood, poikiloderma • Skin cancers in first decade of life • Basal cell carcinoma • Squamous cell carcinoma • Melanoma • Brain tumors |
| ERCC excision repair 3, TFIIH core complex helicase subunit (ERCC3) ERCC excision repair 4, endonuclease catalytic subunit (ERCC4) ERCC excision repair 5, endonuclease (ERCC5) DNA polymerase eta (POLH) XPA, DNA damage recognition, and repair factor (XPA) |
• Lung cancer • Neurological abnormalities |