PMID- 10087940 OWN - NLM STAT- MEDLINE DCOM- 19990407 LR - 20220331 IS - 0165-4608 (Print) IS - 0165-4608 (Linking) VI - 109 IP - 2 DP - 1999 Mar TI - Fluorescence in situ hybridization analysis shows the frequent occurrence of 14q32.3 rearrangements with involvement of immunoglobulin switch regions in myeloma cell lines. PG - 99-107 AB - In many B-cell malignancies, 14q32.3 chromosomal rearrangements involving the immunoglobulin heavy chain (IgH) locus have been shown to be pathognomonic for the disease. Although in myeloma heterogeneous and complex karyotypes are found, 14q32.3 translocations are prominent. However, owing to the telomeric position of the IgH locus, 14q32.3 translocations may be easily missed. We established fluorescence in situ hybridization (FISH) assays on chromosomes and DNA fibers to determine both the occurrence of 14q32.3 rearrangements in myeloma cell lines and the precise localization of the breakpoints in the IgH locus. Our results show that 14q32.3 chromosomal rearrangements are present in almost every myeloma cell line analyzed (17 of 19, 89%). Breakpoint analysis of the lines harboring one or more 14q32.3 rearrangements with the use of fiber-FISH revealed the involvement of switch regions in the IgH locus in 11 of 17 cell lines. Remarkably, pseudogamma genes without switch regions were involved in 3 of 17 cell lines, all derived from IgA myelomas. Three of 17 cell lines contained breakpoints outside a switch or immunoglobulin heavy chain constant region. The almost ubiquitous presence of 14q32.3 rearrangements suggests an obligatory role in the development of myeloma. The high incidence of breakpoints involving switch regions indicates an oncogenic event in a late stage of B-cell differentiation. FAU - Kuipers, J AU - Kuipers J AD - Department of Immunology, Utrecht University, The Netherlands. FAU - Vaandrager, J W AU - Vaandrager JW FAU - Weghuis, D O AU - Weghuis DO FAU - Pearson, P L AU - Pearson PL FAU - Scheres, J AU - Scheres J FAU - Lokhorst, H M AU - Lokhorst HM FAU - Clevers, H AU - Clevers H FAU - Bast, B J AU - Bast BJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Genet Cytogenet JT - Cancer genetics and cytogenetics JID - 7909240 RN - 0 (Immunoglobulin Heavy Chains) SB - IM MH - Chromosome Aberrations MH - *Chromosomes, Human, Pair 14 MH - Gene Frequency MH - Humans MH - Immunoglobulin Class Switching/*genetics MH - Immunoglobulin Heavy Chains/biosynthesis/genetics MH - *In Situ Hybridization, Fluorescence MH - Metaphase MH - Multiple Myeloma/*genetics/pathology MH - Tumor Cells, Cultured EDAT- 1999/03/24 00:00 MHDA- 1999/03/24 00:01 CRDT- 1999/03/24 00:00 PHST- 1999/03/24 00:00 [pubmed] PHST- 1999/03/24 00:01 [medline] PHST- 1999/03/24 00:00 [entrez] AID - S0165460898001575 [pii] AID - 10.1016/s0165-4608(98)00157-5 [doi] PST - ppublish SO - Cancer Genet Cytogenet. 1999 Mar;109(2):99-107. doi: 10.1016/s0165-4608(98)00157-5.