Our findings support a role of POT1 germline mutations in cancer predisposition beyond melanoma development, suggesting a broader phenotype of the POT1-associated tumor predisposition syndrome that might also include thyroid cancer as well as possibly other malignant tumors.
Li-Fraumeni syndrome (LFS) is an autosomal dominant, inherited tumor predisposition syndrome associated with heterozygous germline mutations in the TP53 gene.
Sporadic cases are associated with KIAA1549:BRAF fusion rearrangements, while 15-20% of children develop PA in the context of the neurofibromatosis 1 (NF1) inherited tumor predisposition syndrome.
Sporadic cases are associated with KIAA1549:BRAF fusion rearrangements, while 15-20% of children develop PA in the context of the neurofibromatosis 1 (NF1) inherited tumor predisposition syndrome.
Tuberous sclerosis complex (TSC), an inherited tumor predisposition syndrome associated with mutations in TSC1 or TSC2, affects ∼1 in 6,000 individuals.
The ERM subgroup member merlin/schwannomin is inactivated in the tumor-predisposition syndrome neurofibromatosis 2 (NF2), and the prototypic 4.1 subgroup member, Protein 4.1B, has been implicated in the molecular pathogenesis of breast, lung and brain cancers.
The ERM subgroup member merlin/schwannomin is inactivated in the tumor-predisposition syndrome neurofibromatosis 2 (NF2), and the prototypic 4.1 subgroup member, Protein 4.1B, has been implicated in the molecular pathogenesis of breast, lung and brain cancers.
DICER1 mutations are known to be present in a majority of PPBs with or without a germline mutation and may be part of a familial tumor predisposition syndrome.
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene.
Fumarate hydratase: (FH) was recently identified as the predisposing gene for a tumor predisposition syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC) (MIM 605839).
As BIMTs can serve as an early marker of the BAP1 hereditary tumor predisposition syndrome, we believe a need exists for a more comprehensive combined clinical and pathological approach for BIMT identification.
As our BCCs probably developed independently from the BAP1-TPDS and UMs frequently show loss of nuclear BAP1 staining, genetic analysis is mandatory to diagnose this syndrome.
Germline mutations of the oncosuppressor gene breast cancer 1-associated protein 1 (BAP1) were recently related to an autosomal-dominant tumor predisposition syndrome (BAP1-TPDS), characterized by uveal melanoma, malignant mesothelioma (MM), cutaneous melanoma, and other malignancies.
It appears that nearly all patients with germline BAP1 mutations develop malignancies by age 55, most frequently uveal melanoma, cutaneous melanoma, pleural or peritoneal malignant mesothelioma, or renal cell carcinoma, although other cancers have also been associated with BAP1TPDS.
Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated cancer syndrome.