Derivative Chromosome 3 Loss from t(3;6)(q12;q14) Followed by Differential VHL Mutations Underlie Multifocal ccRCC

Kosuke Mizutani, Shigeaki Yokoi, Seiya Sawada, Ippei Sakamoto, Koji Kameyama, Shingo Kamei, Kouseki Hirade, Seiji Sugiyama, Kengo Matsunaga, Tetsuya Yamada, Yasutaka Kato, Hiroshi Nishihara, Satoshi Ishihara, Takashi Deguchi

研究成果: Article査読


Background/Aim: The Von Hippel-Lindau (VHL) gene encodes a protein (pVHL) that plays an important role in proteasome degradation of hypoxia inducible factor α (HIFα) through E3 activation. Accumulation of HIFα by loss of functional pVHL promotes tumorigenesis, thus, VHL has tumor suppressor gene capability in clear cell renal cell carcinoma (ccRCC). VHL is the most frequently mutated gene in ccRCC. The complete loss of VHL is mainly achieved by loss of chromosome 3p, which has a VHL coding region in combination with mutation or hypermethylation of the remaining copy of VHL. Given the risk of constitutional chromosome 3 translocation for RCC, it is important to detect the translocation and understand the mechanism underlying the development of multifocal ccRCC. Case Report: A 67- year-old female patient diagnosed with multifocal RCC underwent robot-assisted partial nephrectomy (RAPN) for three kidney tumors. A cancer gene panel test using next generation sequencing (NGS) detected differential VHL mutations (c.533T>G; p.L178R, c.465_466insTA; p.T157Ifs*3, c.343C>A; p.H115N), while VHL mutation was not detected in peripheral blood DNA. A tendency toward copy number loss of genes on der(3) was also detected in all tumors, but not in the germline one. A karyotype analysis revealed a germline translocation between 3 and 6, t(3;6)(q12;q14). Conclusion: Chromosome 3 translocation and loss of derivative chromosome containing 3p and subsequent somatic differential VHL mutations in this case strongly support the previously proposed three-step model to explain the development of familial conventional ccRCC.

ジャーナルCancer Genomics and Proteomics
出版ステータスPublished - 2022 11月

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 遺伝学
  • 癌研究


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