title: Interphase FISH assays for the detection of translocations with breakpoints in immunoglobulin light chain loci.
abstract: Many B-cell malignancies bear chromosomal translocations juxtaposing immunoglobulin (IG) genes with oncogenes, resulting in deregulated expression of the latter. Translocations affecting the IG heavy chain (IGH) locus in chromosomal region 14q32 are most prevalent. However, variant translocations involving the IG kappa (IGK) locus in 2p12 or the IG lambda (IGL) locus in 22q11 occur recurrently in B-cell neoplasias. No routine methods for the detection of all breakpoints involving IG light chain loci independently of the translocation partner have been described. For this reason, we have designed 2 novel interphase fluorescence in situ hybridization (FISH) assays using differentially labeled probes flanking the IGK and IGL locus, respectively. Based on extensive control studies, the diagnostic thresholds for the detection of breakpoints were set at 0.3% for IGK and 1.4% for IGL. Fifteen cases of B-cell malignancies with cytogenetically detectable chromosomal abnormalities in 2p11-14 were investigated with the FISH assay for IGK. Breakpoints affecting the IGK locus were detected in 7 cases including all 4 variant Burkitt's translocations t(2;8)(p12;q24) and a variant BCL2-associated translocation t(2;18)(p12;q21). Other translocation partners were chromosome bands 7q21 and 16q24. Ten cases with abnormalities in 22q11-12 were investigated with the FISH assay for IGL. Breakpoints in the IGL locus were diagnosed in 7 cases including both variant Burkitt's translocations t(8;22)(q24;q11) and a t(3;22)(q27;q11) involving the BCL6 locus. Other translocation partners were 2p13-14, 4q13 and 16p12. Our results show that these FISH assays provide flexible, simple and reliable tools in the diagnosis and characterization of genetic changes in B-cell malignancies.
authors.affiliation: Institute of Human Genetics, University Hospital Kiel, Germany.
authors.forename: José I
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Werner
authors.initials: W
authors.lastname: Grote
authors.forename: José A
authors.initials: JA
authors.lastname: Martinez-Climent
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Novo
authors.forename: María J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14; D002885:Chromosomes, Human, Pair 16; D002889:Chromosomes, Human, Pair 2; D002892:Chromosomes, Human, Pair 22; D002894:Chromosomes, Human, Pair 4; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic