Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acral lentiginous melanoma (ALM) is the less common subtype with singular characterization. TERT (human telomerase reverse transcriptase) promoter mutations have being described as recurrent in melanomas and infrequent in ALM, but their real incidence and clinical relevance is unclear. The objectives of this study were to describe the prevalence of TERT promoter mutations in ALM, and correlate with the molecular profile of other drive genes and clinical features. Sixty-one samples from 48 patients with ALM were analyzed. After DNA isolation, the mutation profiles of the hotspot region of BRAF, NRAS, KIT, PDGFRA, and TERT genes were determined by PCR amplification followed by direct Sanger sequencing. KIT, PDGFRA, and VEGFR2 gene amplification was performed by quantitative PCR. Clinical information such as survival, clinical stage, and Breslow tumor classification were obtained from medical records. TERT promoter mutations were found in 9.3% of the cases, BRAF in 10.3%, NRAS in 7.5%, KIT in 20.7%, and PDGFRA in 14.8% of ALM. None of the cases showed KIT, PDGFRA, or VEGFR2 gene amplification. We found an association between KIT mutations and advanced Clark level (IV and V, P=0.043) and TERT promoter mutations with low mitotic index. No other significant associations were observed between mutation profile and patients' clinical features nor survival rates. Oncogenic TERT promoter mutations are present in a fraction of ALMs. No relevant associations were found between TERT mutation status and clinical/molecular features nor survival. Mutations of KIT and PDGFRA are the most common genetic alterations, and they can be therapeutic targets for these patients.
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PMID:Molecular profiling, including TERT promoter mutations, of acral lentiginous melanomas. 2670 72

Acral lentiginous melanoma (ALM) is the most common type of malignant melanoma (MM) in Asians, Afro-Americans and Middle-Easterners. It represents 1.5-10% of all MM cases, being the most common histological type of MM arising on palms, soles and nail apparatus, which is more generically defined as acral MM. To date no risk factors have been officially established, however a history of trauma may be involved in the pathogenesis of acral MM. This shows heterogeneous clinical features and frequently presents with advanced stage and aggressive behavior, often as a result of misdiagnosis or delayed identification. Dermoscopy is helpful for an early diagnosis of ALM: the most characteristic dermoscopic patterns are the parallel ridge and the irregular diffuse pigmentation. On histopathology ALM displays a lentiginous growth pattern, with melanocytes arranged as solitary units along the basilar epidermis, without notable pagetoid growth in the early stage. Not all acral MMs present a lentiginous pattern: superficial spreading melanoma and nodular melanoma patterns are also possible. Novel studies investigating the biologic characteristics of acral MM reported variable results: the overall mutational rates ranged respectively between 8.5% and 23% for KIT, between 3.6% and 33.3% for BRAF and between 3% and 47% for NRAS in ALMs. Increasing attention has been recently given to other genes, such as telomerase reverse transcriptase, platelet-derived growth factor receptor alfa and cyclin D1. Larger molecular investigations urge to describe the molecular profile of acral MM, to allow the development of specific targeted therapies.
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PMID:Acral melanoma: correlating the clinical presentation to the mutational status. 2951 74