Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma

Nicole Y. Fang, Timothy Charles Greiner, Dennis D. Weisenburger, Wing C. Chan, Julie Marie Vose, Lynette M Smith, James Olen Armitage, R. Aeryn Mayer, Brian L. Pike, Francis S. Collins, Joseph G. Hacia

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Abstract

Mutations have been described in the ataxia telangiectasia mutated (ATM) gene in small numbers of cases of lymphoid neoplasia. However, surveys of the ATM mutation status in lymphoma have been limited due to the large size (62 exons) and complex mutational spectrum of this gene. We have used microarray-based assays with 250,000 oligonucleotides to screen lymphomas from 120 patients for all possible ATM coding and splice junction mutations. The subtypes included were diffuse large B cell, mantle cell, immunoblastic large B cell, follicular, posttransplant lymphoproliferative disorder, and peripheral T cell lymphoma. We found the highest percentage of ATM mutations within the mantle cell (MCL) subtype (43%, 12 of 28 cases), followed by a lower level (10% of cases) in the other subtypes. A frame-shift ATM mutation was found in one peripheral T cell lymphoma patient. In six MCL cases examined, four ATM variants were due to somatic mutation in the tumor cells whereas two others seemed to be germ-line in origin. There was no difference in p53 mutation status in the ATM mutant and wild-type groups of MCL. There was no statistically significant difference in the median overall survival of patients with wild-type vs. mutated ATM in MCL. Additional mutational and functional analyses are needed to determine whether ATM mutations contribute to the development and progression of MCL or are just the consequence of genomic instability in MCL.

Original languageEnglish (US)
Pages (from-to)5372-5377
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number9
DOIs
StatePublished - Apr 29 2003

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Mantle-Cell Lymphoma
Ataxia Telangiectasia
Oligonucleotide Array Sequence Analysis
Mutation
Peripheral T-Cell Lymphoma
Lymphoma
B-Lymphocytes
Lymphoproliferative Disorders
Genomic Instability
Germ Cells
Oligonucleotides
Genes
Exons
Neoplasms
Survival

ASJC Scopus subject areas

  • General

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Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma. / Fang, Nicole Y.; Greiner, Timothy Charles; Weisenburger, Dennis D.; Chan, Wing C.; Vose, Julie Marie; Smith, Lynette M; Armitage, James Olen; Mayer, R. Aeryn; Pike, Brian L.; Collins, Francis S.; Hacia, Joseph G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 9, 29.04.2003, p. 5372-5377.

Research output: Contribution to journalArticle

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abstract = "Mutations have been described in the ataxia telangiectasia mutated (ATM) gene in small numbers of cases of lymphoid neoplasia. However, surveys of the ATM mutation status in lymphoma have been limited due to the large size (62 exons) and complex mutational spectrum of this gene. We have used microarray-based assays with 250,000 oligonucleotides to screen lymphomas from 120 patients for all possible ATM coding and splice junction mutations. The subtypes included were diffuse large B cell, mantle cell, immunoblastic large B cell, follicular, posttransplant lymphoproliferative disorder, and peripheral T cell lymphoma. We found the highest percentage of ATM mutations within the mantle cell (MCL) subtype (43{\%}, 12 of 28 cases), followed by a lower level (10{\%} of cases) in the other subtypes. A frame-shift ATM mutation was found in one peripheral T cell lymphoma patient. In six MCL cases examined, four ATM variants were due to somatic mutation in the tumor cells whereas two others seemed to be germ-line in origin. There was no difference in p53 mutation status in the ATM mutant and wild-type groups of MCL. There was no statistically significant difference in the median overall survival of patients with wild-type vs. mutated ATM in MCL. Additional mutational and functional analyses are needed to determine whether ATM mutations contribute to the development and progression of MCL or are just the consequence of genomic instability in MCL.",
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AU - Fang, Nicole Y.

AU - Greiner, Timothy Charles

AU - Weisenburger, Dennis D.

AU - Chan, Wing C.

AU - Vose, Julie Marie

AU - Smith, Lynette M

AU - Armitage, James Olen

AU - Mayer, R. Aeryn

AU - Pike, Brian L.

AU - Collins, Francis S.

AU - Hacia, Joseph G.

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