Recurrent somatic loss of TNFRSF14 in classical Hodgkin lymphoma

Stephen J. Salipante, Andrew Adey, Anju Thomas, Choli Lee, Yajuan J. Liu, Akash Kumar, Alexandra P. Lewis, David Wu, Jonathan R. Fromm, Jay Shendure

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Investigation of the genetic lesions underlying classical Hodgkin lymphoma (CHL) has been challenging due to the rarity of Hodgkin and Reed-Sternberg (HRS) cells, the pathognomonic neoplastic cells of CHL. In an effort to catalog more comprehensively recurrent copy number alterations occurring during oncogenesis, we investigated somatic alterations involved in CHL using whole-genome sequencing-mediated copy number analysis of purified HRS cells. We performed low-coverage sequencing of small numbers of intact HRS cells and paired non-neoplastic B lymphocytes isolated by flow cytometric cell sorting from 19 primary cases, as well as two commonly used HRS-derived cell lines (KM-H2 and L1236). We found that HRS cells contain strikingly fewer copy number abnormalities than CHL cell lines. A subset of cases displayed nonintegral chromosomal copy number states, suggesting internal heterogeneity within the HRS cell population. Recurrent somatic copy number alterations involving known factors in CHL pathogenesis were identified (REL, the PD-1 pathway, and TNFAIP3). In eight cases (42%) we observed recurrent copy number loss of chr1:2,352,236-4,574,271, a region containing the candidate tumor suppressor TNFRSF14. Using flow cytometry, we demonstrated reduced TNFRSF14 expression in HRS cells from 5 of 22 additional cases (23%) and in two of three CHL cell lines. These studies suggest that TNFRSF14 dysregulation may contribute to the pathobiology of CHL in a subset of cases.

Original languageEnglish (US)
Pages (from-to)278-287
Number of pages10
JournalGenes Chromosomes and Cancer
Volume55
Issue number3
DOIs
StatePublished - Mar 1 2016

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Recurrent somatic loss of TNFRSF14 in classical Hodgkin lymphoma'. Together they form a unique fingerprint.

  • Cite this

    Salipante, S. J., Adey, A., Thomas, A., Lee, C., Liu, Y. J., Kumar, A., Lewis, A. P., Wu, D., Fromm, J. R., & Shendure, J. (2016). Recurrent somatic loss of TNFRSF14 in classical Hodgkin lymphoma. Genes Chromosomes and Cancer, 55(3), 278-287. https://doi.org/10.1002/gcc.22331