PMID- 30393007 OWN - NLM STAT- MEDLINE DCOM- 20190429 LR - 20190429 IS - 2210-7762 (Print) VI - 228-229 DP - 2018 Dec TI - Assessing genome-wide copy number aberrations and copy-neutral loss-of-heterozygosity as best practice: An evidence-based review from the Cancer Genomics Consortium working group for plasma cell disorders. PG - 184-196 LID - S2210-7762(18)30076-0 [pii] LID - 10.1016/j.cancergen.2018.07.002 [doi] AB - BACKGROUND: Plasma cell neoplasms (PCNs) encompass a spectrum of disorders including monoclonal gammopathy of undetermined significance, smoldering myeloma, plasma cell myeloma, and plasma cell leukemia. Molecular subtypes have been defined by recurrent cytogenetic abnormalities and somatic mutations that are prognostic and predictive. Karyotype and fluorescence in situ hybridization (FISH) have historically been used to guide management; however, new technologies and markers raise the need to reassess current testing algorithms. METHODS: We convened a panel of representatives from international clinical laboratories to capture current state-of-the-art testing from published reports and to put forward recommendations for cytogenomic testing of plasma cell neoplasms. We reviewed 65 papers applying FISH, chromosomal microarray (CMA), next-generation sequencing, and gene expression profiling for plasma cell neoplasm diagnosis and prognosis. We also performed a survey of our peers to capture current laboratory practice employed outside our working group. RESULTS: Plasma cell enrichment is widely used prior to FISH testing, most commonly by magnetic bead selection. A variety of strategies for direct, short- and long-term cell culture are employed to ensure clonal representation for karyotyping. Testing of clinically-informative 1p/1q, del(13q) and del(17p) are common using karyotype, FISH and, increasingly, CMA testing. FISH for a variety of clinically-informative balanced IGH rearrangements is prevalent. Literature review found that CMA analysis can detect abnormalities in 85-100% of patients with PCNs; more specifically, in 5-53% (median 14%) of cases otherwise normal by FISH and cytogenetics. CMA results in plasma cell neoplasms are usually complex, with alteration counts ranging from 1 to 74 (median 10-20), primarily affecting loci not covered by FISH testing. Emerging biomarkers include structural alterations of MYC as well as somatic mutations of KRAS, NRAS, BRAF, and TP53. Together, these may be measured in a comprehensive manner by a combination of newer technologies including CMA and next-generation sequencing (NGS). Our survey suggests most laboratories have, or are soon to have, clinical CMA platforms, with a desire to move to NGS assays in the future. CONCLUSION: We present an overview of current practices in plasma cell neoplasm testing as well as an algorithm for integrated FISH and CMA testing to guide treatment of this disease. CI - Copyright (c) 2018. Published by Elsevier Inc. FAU - Pugh, Trevor J AU - Pugh TJ AD - Princess Margaret Cancer Centre, University Health Network; Ontario Institute for Cancer Research; and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. Electronic address: trevor.pugh@utoronto.ca. FAU - Fink, James M AU - Fink JM AD - Department of Laboratory Medicine and Pathology, Hennepin County Medical Center, Minneapolis, MN, USA. FAU - Lu, Xinyan AU - Lu X AD - Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. FAU - Mathew, Susan AU - Mathew S AD - Department of Pathology, Weill Cornell Medicine, New York, NY, USA. FAU - Murata-Collins, Joyce AU - Murata-Collins J AD - Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA. FAU - Willem, Pascale AU - Willem P AD - Department of Haematology and Molecular Medicine, Faculty of Health Sciences, University of the Witwatersrand and the National Health Laboratory Service, Johannesburg, South Africa. FAU - Fang, Min AU - Fang M AD - Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA. Electronic address: mfang@fredhutch.org. CN - Cancer Genomics Consortium Plasma Cell Disorders Working Group LA - eng PT - Journal Article PT - Review DEP - 20181005 PL - United States TA - Cancer Genet JT - Cancer genetics JID - 101539150 RN - 0 (Biomarkers, Tumor) SB - IM MH - Biomarkers, Tumor/genetics MH - *DNA Copy Number Variations MH - *Evidence-Based Medicine MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Loss of Heterozygosity MH - Neoplasms, Plasma Cell/*genetics OTO - NOTNLM OT - Chromosomal microarray testing OT - Cytogenetics OT - Guidelines OT - Multiple myeloma OT - Next-generation sequencing OT - Plasma cell disorders OT - Plasma cell myeloma OT - Recommendations EDAT- 2018/11/06 06:00 MHDA- 2019/04/30 06:00 CRDT- 2018/11/06 06:00 PHST- 2018/03/13 00:00 [received] PHST- 2018/07/16 00:00 [revised] PHST- 2018/07/30 00:00 [accepted] PHST- 2018/11/06 06:00 [pubmed] PHST- 2019/04/30 06:00 [medline] PHST- 2018/11/06 06:00 [entrez] AID - S2210-7762(18)30076-0 [pii] AID - 10.1016/j.cancergen.2018.07.002 [doi] PST - ppublish SO - Cancer Genet. 2018 Dec;228-229:184-196. doi: 10.1016/j.cancergen.2018.07.002. Epub 2018 Oct 5.