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Published on: October 30, 2013
Variants of Human Mucin Genes in Clear Cell Renal Cell Carcinoma and their Potential Prognostic and Predictive Values
Jamal Zekri1,2, Mohammed A Baghdadi1, Abdelrazak Meliti1
1King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
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.
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