Genetic Basis of Hepatosplenic T Cell Lymphoma (HSTL)

Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001003246	Whole exome sequencing of hepatosplenic T cell lymphoma (HSTL) tumors, paired normals, and cell lines, including (1) 68 exome capture, paired-end Illumina Hiseq sequencing, BAM files from HSTL tumor samples, (2) 20 exome capture, paired-end Illumina Hiseq sequencing, BAM files from HSTL paired normal samples, and (3) 2 exome capture, paired-end Illumina Hiseq sequencing, BAM files from HSTL cell lines.	Illumina HiSeq 2500	90

Publications	Citations
The Genetic Basis of Hepatosplenic T-cell Lymphoma. McKinney M, Moffitt AB, Gaulard P, Travert M, De Leval L, Nicolae A, Raffeld M, Jaffe ES, Pittaluga S, Xi L, Heavican T, Iqbal J, Belhadj K, Delfau-Larue MH, Fataccioli V, Czader MB, Lossos IS, Chapman-Fredricks JR, Richards KL, Fedoriw Y, Ondrejka SL, Hsi ED, Low L, Weisenburger D, Chan WC, Mehta-Shah N, Horwitz S, Bernal-Mizrachi L, Flowers CR, Beaven AW, Parihar M, Baseggio L, Parrens M, Moreau A, Sujobert P, Pilichowska M, Evens AM, Chadburn A, Au-Yeung RK, Srivastava G, Choi WW, Goodlad JR, Aurer I, Basic-Kinda S, Gascoyne RD, Davis NS, Li G, Zhang J, Rajagopalan D, Reddy A, Love C, Levy S, Zhuang Y, Datta J, Dunson DB, Davé SS. Cancer Discov 7: 2017 369-379	89

Publications

Citations

The Genetic Basis of Hepatosplenic T-cell Lymphoma.
McKinney M, Moffitt AB, Gaulard P, Travert M, De Leval L, Nicolae A, Raffeld M, Jaffe ES, Pittaluga S, Xi L, Heavican T, Iqbal J, Belhadj K, Delfau-Larue MH, Fataccioli V, Czader MB, Lossos IS, Chapman-Fredricks JR, Richards KL, Fedoriw Y, Ondrejka SL, Hsi ED, Low L, Weisenburger D, Chan WC, Mehta-Shah N, Horwitz S, Bernal-Mizrachi L, Flowers CR, Beaven AW, Parihar M, Baseggio L, Parrens M, Moreau A, Sujobert P, Pilichowska M, Evens AM, Chadburn A, Au-Yeung RK, Srivastava G, Choi WW, Goodlad JR, Aurer I, Basic-Kinda S, Gascoyne RD, Davis NS, Li G, Zhang J, Rajagopalan D, Reddy A, Love C, Levy S, Zhuang Y, Datta J, Dunson DB, Davé SS. Cancer Discov 7: 2017 369-379