Next-generation sequencing of uveal melanoma with clinical and histological correlations: Prognostic value of new mutations in the PI3K/AKT/mTOR pathway.

BACKGROUND: Uveal melanoma (UM) is the eye's most common primary malignancy and there are no effective therapies for disseminated disease. It is important to try to know the patient's prognosis. The aim of this study was to reflect genetic variants, studied using NGS, of a series of 69 cases of UM and its correlation with histopathology and clinical progression. METHODS: We performed targeted NGS using a 519-gene panel. RESULTS: There were selected 28 different mutated genes, showing a total of 231 genetic variants that affected the function of the protein. The most common secondary mutations occurred in SF3B1 (in 26%), followed by BAP1 (in 23%), LRP1B (22%) and FGFR4 (20%). BAP1 mutation was associated with a greater likelihood of metastases and with greater presence of epithelioid cells. LRP1B was also associated with presence of epithelioid cells SF3B1 mutation was significantly associated with a spindle morphology. We found variants in the RAD51B, TOP2A, PTPRD, TSC2, DHX9, PDK1 and MTOR that have not been previously reported in consulted databases. The presence of a mutation in: CHEK2, DHX9 and PDK1 was associated with metastases. CONCLUSIONS: BAP1 is the most solid biomarker of a poor prognosis in UM and mutations can be detected using NGS. SF3B1 is associated with the spindle cell subtype of UM, which gives it probably a favourable prognostic value. Our study suggests that mutations in DHX9 and PDK1 can have prognostic value. These potential biomarkers are related to the PI3K/AKT/mTOR pathway and makes them candidates for developing new directed therapies.

Molecular findings of nasopharyngeal carcinoma in a European population.

OBJECTIVE: To explore biomolecular characteristics of a group of patients with nasopharyngeal carcinoma from European (Spanish) hospitals, addressing the pathogenesis of the tumor and the response to treatment. STUDY DESIGN: Cyclin D1 and p16 expression were evaluated immunohistochemically in 33 tissue samples of nasopharyngeal carcinoma. CCDN1 gene amplification and p16 gene deletion were studied by fluorescence in situ hybridization. Patient clinical data were examined, and tissues were evaluated histologically using hematoxylin-eosin staining. RESULTS: Cyclin D1 overexpression was found in 19 cases, and p16 expression was undetected in 30 cases. An association was observed between impaired p16 expression and cyclin D1 overexpression (p = 0.034). Eleven patients displayed p16 gene deletion and CCDN1 gene amplification. CONCLUSION: Cyclin D1 overexpression and CCDN1 amplification, loss of p16 expression and p16 deletion may be among the genetic alterations involved in the pathogenesis of nasopharyngeal carcinoma.