Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing

Andrew L Feldman, Ahmet Dogan, David I Smith, Mark E. Law, Stephen Maxted Ansell, Sarah H. Johnson, Julie C. Porcher, Nazan Özsan, Eric D Wieben, Bruce W. Eckloff, George Vasmatzis

Research output: Contribution to journalArticle

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Abstract

The genetics of peripheral T-cell lymphomas are poorly understood. The most well-characterized abnormalities are translocations involving ALK, occurring in approximately half of anaplastic large cell lymphomas (ALCLs). To gain insight into the genetics of ALCLs lacking ALK translocations, we combined mate-pair DNA library construction, massively parallel ("Next Generation") sequencing, and a novel bioinformatic algorithm. We identified a balanced translocation disrupting the DUSP22 phosphatase gene on 6p25.3 and adjoining the FRA7H fragile site on 7q32.3 in a systemic ALK-negative ALCL. Using fluorescence in situ hybridization, we demonstrated that the t(6;7)(p25.3;q32.3) was recurrent in ALK-negative ALCLs. Furthermore, t(6;7)(p25.3; q32.3) was associated with down-regulation of DUSP22 and up-regulation of MIR29 microRNAs on 7q32.3. These findings represent the first recurrent translocation reported in ALK-negative ALCL and highlight the utility of massively parallel genomic sequencing to discover novel translocations in lymphoma and other cancers.

Original languageEnglish (US)
Pages (from-to)915-919
Number of pages5
JournalBlood
Volume117
Issue number3
DOIs
StatePublished - Jan 20 2011

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Anaplastic Large-Cell Lymphoma
High-Throughput Nucleotide Sequencing
T-cells
Bioinformatics
MicroRNAs
Gene Library
Phosphoric Monoester Hydrolases
Genes
Fluorescence
Peripheral T-Cell Lymphoma
Computational Biology
Fluorescence In Situ Hybridization
Lymphoma
Up-Regulation
Down-Regulation
Genetics
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. / Feldman, Andrew L; Dogan, Ahmet; Smith, David I; Law, Mark E.; Ansell, Stephen Maxted; Johnson, Sarah H.; Porcher, Julie C.; Özsan, Nazan; Wieben, Eric D; Eckloff, Bruce W.; Vasmatzis, George.

In: Blood, Vol. 117, No. 3, 20.01.2011, p. 915-919.

Research output: Contribution to journalArticle

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abstract = "The genetics of peripheral T-cell lymphomas are poorly understood. The most well-characterized abnormalities are translocations involving ALK, occurring in approximately half of anaplastic large cell lymphomas (ALCLs). To gain insight into the genetics of ALCLs lacking ALK translocations, we combined mate-pair DNA library construction, massively parallel ({"}Next Generation{"}) sequencing, and a novel bioinformatic algorithm. We identified a balanced translocation disrupting the DUSP22 phosphatase gene on 6p25.3 and adjoining the FRA7H fragile site on 7q32.3 in a systemic ALK-negative ALCL. Using fluorescence in situ hybridization, we demonstrated that the t(6;7)(p25.3;q32.3) was recurrent in ALK-negative ALCLs. Furthermore, t(6;7)(p25.3; q32.3) was associated with down-regulation of DUSP22 and up-regulation of MIR29 microRNAs on 7q32.3. These findings represent the first recurrent translocation reported in ALK-negative ALCL and highlight the utility of massively parallel genomic sequencing to discover novel translocations in lymphoma and other cancers.",
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