生物
染色体易位
肾细胞癌
遗传学
癌症研究
计算生物学
进化生物学
内科学
基因
医学
作者
Mingkee Achom,Ananthan Sadagopan,Chunyang Bao,Fiona McBride,Jiao Li,Prathyusha Konda,Richard W. Tourdot,Qingru Xu,Maria Nakhoul,Daniel S. Gallant,Usman Ali Ahmed,Jillian O’Toole,Dory Freeman,Gwo‐Shu Mary Lee,Jonathan L. Hecht,Eric Kauffman,David J. Einstein,Toni K. Choueiri,Cheng‐Zhong Zhang,Srinivas R. Viswanathan
出处
期刊:PubMed
日期:2024-08-14
标识
DOI:10.1016/j.cell.2024.07.038
摘要
Xp11 translocation renal cell carcinoma (tRCC) is a rare, female-predominant cancer driven by a fusion between the transcription factor binding to IGHM enhancer 3 (TFE3) gene on chromosome Xp11.2 and a partner gene on either chromosome X (chrX) or an autosome. It remains unknown what types of rearrangements underlie TFE3 fusions, whether fusions can arise from both the active (chrXa) and inactive X (chrXi) chromosomes, and whether TFE3 fusions from chrXi translocations account for the female predominance of tRCC. To address these questions, we performed haplotype-specific analyses of chrX rearrangements in tRCC whole genomes. We show that TFE3 fusions universally arise as reciprocal translocations and that oncogenic TFE3 fusions can arise from chrXi:autosomal translocations. Female-specific chrXi:autosomal translocations result in a 2:1 female-to-male ratio of TFE3 fusions involving autosomal partner genes and account for the female predominance of tRCC. Our results highlight how X chromosome genetics constrains somatic chrX alterations and underlies cancer sex differences.
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