title: Genome wide SNP array identified multiple mechanisms of genetic changes in Waldenstrom macroglobulinemia.
abstract: SNP array (SNPa) was developed to detect copy number alteration (CNA) and loss of heterozygosity (LOH) without copy number changes, CN-LOH. We aimed to identify novel genomic aberrations using SNPa in 31 WM with paired samples. Methylation status and mutation were analyzed on target genes. A total of 61 genetic aberrations were observed, 58 CNA (33 gains, 25 losses) in 58% of patients and CN-LOH in 6% of patients. The CNA were widely distributed throughout the genome, including 12 recurrent regions and identified new cryptic clonal chromosomal lesions that were mapped. Gene set expression analysis demonstrated a relationship between either deletion 6q or gain of chromosome 4 and alteration of gene expression profiling. We then studied methylation status and sought for mutations in altered regions on target genes. We observed methylation of DLEU7 on chromosome 13 in all patients (n = 12) with WM, and mutations of CD79B/CD79A genes (17q region), a key component of the BCR pathway, in 15% of cases. Most importantly, higher frequency of ≥3 CNA was observed in symptomatic WM. In conclusion, this study expands the view of the genomic complexity of WM, especially in symptomatic WM, including a potentially new mechanism of gene dysfunction, acquired uniparental disomy/CN-LOH. Finally, we have identified new potential target genes in WM, such as DLEU7 and CD79A/B.
authors.affiliation: Service d'Hématologie-Immunologie-Cytogénétique, CH, Valenciennes, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Poulain
authors.forename: Christophe
authors.initials: C
authors.lastname: Roumier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Galiègue-Zouitina
authors.forename: Agnès
authors.initials: A
authors.lastname: Daudignon
authors.forename: Charles
authors.initials: C
authors.lastname: Herbaux
authors.forename: Rachid
authors.initials: R
authors.lastname: Aiijou
authors.forename: Amélie
authors.initials: A
authors.lastname: Lainelle
authors.forename: Natacha
authors.initials: N
authors.lastname: Broucqsault
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bertrand
authors.forename: Salomon
authors.initials: S
authors.lastname: Manier
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
authors.forename: Valérie
authors.initials: V
authors.lastname: Soenen
authors.forename: Sabine
authors.initials: S
authors.lastname: Tricot
authors.forename: Catherine
authors.initials: C
authors.lastname: Roche-Lestienne
authors.forename: Patrick
authors.initials: P
authors.lastname: Duthilleul
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesnel
authors.forename: Pierre
authors.initials: P
authors.lastname: Morel
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051925:CD79 Antigens / Q000235:genetics / Q000378:metabolism; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D005260:Female; D005602:France; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics* / Q000378:metabolism
chemical_list: D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; C482307:DLEU7 protein, human; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins