PMID- 32447782 OWN - NLM STAT- MEDLINE DCOM- 20210818 LR - 20210818 IS - 1098-2264 (Electronic) IS - 1045-2257 (Linking) VI - 59 IP - 10 DP - 2020 Oct TI - High-risk cytogenetics in multiple myeloma: Further scrutiny of deletions within the IGH gene region enhances risk stratification. PG - 569-574 LID - 10.1002/gcc.22874 [doi] AB - Multiple myeloma is a clonal malignancy of plasma cells in the bone marrow. Risk stratification is partly based on cytogenetic findings that include abnormalities of the IGH locus as determined by fluorescence in situ hybridization (FISH), such as rearrangements that result in either standard-risk or high-risk gene fusions. IGH deletions have been evaluated as a group in multiple myeloma patients with respect to cumulative outcomes but have provided limited guidance. Whether these deletions have the potential to result in gene fusions and thus further stratify patients is unknown. We identified 229 IGH deletions in patients referred for plasma cell dyscrasia genetic testing over 5.5 years. Follow-up was conducted on 208 of the deletions with dual fusion FISH probes for standard-risk (IGH-CCND1) and high-risk IGH gene fusions (IGH-FGFR3, IGH-MAF, IGH-MAFB). Of all deletions identified with follow-up, 44 (21%) resulted in a gene fusion as detected by FISH, 15 (7%) of which were fusion partners associated with high-risk multiple myeloma. All fusion-positive 3'-IGH deletions (6 fusions) resulted in high-risk IGH-FGFR3 fusions. Of the 15 high-risk fusion-positive cases, eight were without other high-risk cytogenetic findings. This study is the first to evaluate the presence of IGH gene fusions upon identification of IGH deletions and to characterize the deletion locus. Importantly, these findings indicate that follow-up FISH studies with dual fusion probes should be standard of care when IGH deletions are identified in multiple myeloma. CI - (c) 2020 Wiley Periodicals, Inc. FAU - Smith, Scott C AU - Smith SC AUID- ORCID: 0000-0003-2938-6202 AD - Human Genetics Laboratory, Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Althof, Pamela A AU - Althof PA AD - Human Genetics Laboratory, Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Dave, Bhavana J AU - Dave BJ AD - Human Genetics Laboratory, Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, USA. FAU - Sanmann, Jennifer N AU - Sanmann JN AD - Human Genetics Laboratory, Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, USA. LA - eng PT - Journal Article DEP - 20200619 PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 RN - 0 (Biomarkers, Tumor) RN - 0 (Immunoglobulin Heavy Chains) RN - 0 (Oncogene Proteins, Fusion) SB - IM CIN - Genes Chromosomes Cancer. 2021 Jan;60(1):54. PMID: 32893387 CIN - Genes Chromosomes Cancer. 2021 Jan;60(1):55. PMID: 32949443 MH - Biomarkers, Tumor/genetics MH - *Gene Deletion MH - Genetic Testing/*methods/standards MH - Humans MH - Immunoglobulin Heavy Chains/*genetics MH - In Situ Hybridization, Fluorescence/*methods/standards MH - Multiple Myeloma/*genetics/pathology MH - Oncogene Proteins, Fusion/genetics MH - Sensitivity and Specificity OTO - NOTNLM OT - IGH deletion OT - IGH rearrangement OT - high-risk cytogenetics OT - multiple myeloma OT - plasma cell dyscrasia EDAT- 2020/05/25 06:00 MHDA- 2021/08/19 06:00 CRDT- 2020/05/25 06:00 PHST- 2020/03/31 00:00 [received] PHST- 2020/05/12 00:00 [revised] PHST- 2020/05/14 00:00 [accepted] PHST- 2020/05/25 06:00 [pubmed] PHST- 2021/08/19 06:00 [medline] PHST- 2020/05/25 06:00 [entrez] AID - 10.1002/gcc.22874 [doi] PST - ppublish SO - Genes Chromosomes Cancer. 2020 Oct;59(10):569-574. doi: 10.1002/gcc.22874. Epub 2020 Jun 19.