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A genetic basis for sex differences in Xp11 translocation renal cell carcinoma.
Achom, Mingkee; Sadagopan, Ananthan; Bao, Chunyang; McBride, Fiona; Li, Jiao; Konda, Prathyusha; Tourdot, Richard W; Xu, Qingru; Nakhoul, Maria; Gallant, Daniel S; Ahmed, Usman Ali; O'Toole, Jillian; Freeman, Dory; Lee, Gwo-Shu Mary; Hecht, Jonathan L; Kauffman, Eric C; Einstein, David J; Choueiri, Toni K; Zhang, Cheng-Zhong; Viswanathan, Srinivas R.
Affiliation
  • Achom M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • Sadagopan A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Bao C; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • McBride F; Department of Biomedical Informatics, Blavatnik Institute, Harvard Medical School, Boston, MA 02215, USA.
  • Li J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • Konda P; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
  • Tourdot RW; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biomedical Informatics, Blavatnik Institute, Harvard Medical School, Boston, MA 02215, USA.
  • Xu Q; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Nakhoul M; Department of Informatics & Analytics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Gallant DS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Ahmed UA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • O'Toole J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Freeman D; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Lee GM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Hecht JL; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
  • Kauffman EC; Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA.
  • Einstein DJ; Division of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
  • Choueiri TK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
  • Zhang CZ; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: cheng-zhong_zhang@dfci.harvard.edu.
  • Viswanathan SR; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 0
Cell ; 2024 Aug 14.
Article in En | MEDLINE | ID: mdl-39168126
ABSTRACT
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 chrXiautosomal translocations. Female-specific chrXiautosomal translocations result in a 21 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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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Year: 2024 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Year: 2024 Document type: Article Affiliation country: Country of publication: