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Variants of Human Mucin Genes in Clear Cell Renal Cell Carcinoma and their Potential Prognostic and Predictive Values.
Gulf Journal of Oncology 2023 May
BACKGROUND: There is no reliable prognostic and predictive biomarkers for clear cell renal cell carcinoma (cc-RCC).
METHODS: DNA from 47 cc-RCC tissue samples were sequenced using next generation sequencing and a customized gene panel testing for tumor-driver genes including 19 Mucin genes.
RESULTS: Distinctive variants in 12 Mucin genes were present in all samples. These genes are: MUC2, MUC3A, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC12, MUC16, MUC17, MUC19, and MUC22. The numbers of distinctive and non-distinctive variants were counted for each sample. The median number of variants was 455. High variant number (HVN) (>455) was associated with shorter overall survival compared to low variant number (≤455) [Median 50 months vs. not reached; P=0.041]. In the 11 patients who received anti-angiogenic tyrosine kinase inhibitors (TKIs), HVN was associated with a trend of shorter progression free survival.
CONCLUSION: Alterations in Mucin family genes are common in ccRCC. HVN is associated with worse prognosis and may predict decreased benefit from anti-angiogenic TKIs.
KEY WORDS: Mucin; Variants; Renal cell carcinoma; Biomarker; Tyrosine kinase inhibitors.
METHODS: DNA from 47 cc-RCC tissue samples were sequenced using next generation sequencing and a customized gene panel testing for tumor-driver genes including 19 Mucin genes.
RESULTS: Distinctive variants in 12 Mucin genes were present in all samples. These genes are: MUC2, MUC3A, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC12, MUC16, MUC17, MUC19, and MUC22. The numbers of distinctive and non-distinctive variants were counted for each sample. The median number of variants was 455. High variant number (HVN) (>455) was associated with shorter overall survival compared to low variant number (≤455) [Median 50 months vs. not reached; P=0.041]. In the 11 patients who received anti-angiogenic tyrosine kinase inhibitors (TKIs), HVN was associated with a trend of shorter progression free survival.
CONCLUSION: Alterations in Mucin family genes are common in ccRCC. HVN is associated with worse prognosis and may predict decreased benefit from anti-angiogenic TKIs.
KEY WORDS: Mucin; Variants; Renal cell carcinoma; Biomarker; Tyrosine kinase inhibitors.
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