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Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma.

ABSTRACT: Fluorescence in situ hybridization (FISH) is currently the gold-standard assay to detect recurrent genomic abnormalities of prognostic significance in multiple myeloma (MM). Since most translocations in MM involve a position effect with heterogeneous breakpoints, we hypothesize that FISH has the potential to miss translocations involving these regions. We evaluated 70 bone marrow samples from patients with plasma cell dyscrasia by FISH and whole-genome mate-pair sequencing (MPseq). Thirty cases (42.9%) displayed at least one instance of discordance between FISH and MPseq for each primary and secondary abnormality evaluated. Nine cases had abnormalities detected by FISH that went undetected by MPseq including 6 tetraploid clones and three cases with missed copy number abnormalities. In contrast, 19 cases had abnormalities detected by MPseq that went undetected by FISH. Seventeen were MYC rearrangements and two were 17p deletions. MPseq identified 36 MYC abnormalities and 17 (50.0% of MYC abnormal group with FISH results) displayed a false negative FISH result. MPseq identified 10 cases (14.3%) with IgL rearrangements, a recent marker of poor outcome, and 10% with abnormalities in genes associated with lenalidomide response or resistance. In summary, MPseq was superior in the characterization of rearrangement complexity and identification of secondary abnormalities demonstrating increased clinical value compared to FISH.

SUBMITTER: Smadbeck J

PROVIDER: S-EPMC6914798 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma.

Smadbeck James J Peterson Jess F JF Pearce Kathryn E KE Pitel Beth A BA Figueroa Andrea Lebron AL Timm Michael M Jevremovic Dragan D Shi Min M Stewart A Keith AK Braggio Esteban E Riggs Daniel L DL Bergsagel P Leif PL Vasmatzis George G Kearney Hutton M HM Hoppman Nicole L NL Ketterling Rhett P RP Kumar Shaji S Rajkumar S Vincent SV Greipp Patricia T PT Baughn Linda B LB

Blood cancer journal 20191216 12

Fluorescence in situ hybridization (FISH) is currently the gold-standard assay to detect recurrent genomic abnormalities of prognostic significance in multiple myeloma (MM). Since most translocations in MM involve a position effect with heterogeneous breakpoints, we hypothesize that FISH has the potential to miss translocations involving these regions. We evaluated 70 bone marrow samples from patients with plasma cell dyscrasia by FISH and whole-genome mate-pair sequencing (MPseq). Thirty cases ...[more]

PMID: 31844041

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Project description:Multiple myeloma (MM) is an uncontrolled proliferation of plasma cells and these cells play an important role in the immune system. In this research, we retrospectively analyzed cytogenetic abnormalities in 381 patients with MM. Conventional cytogenetic analysis was successful in 354 patients (92.9%). Chromosomal abnormalities were detected in 31.9% (113/354) and 45.8% (116/253) of patients screened with conventional cytogenetics and FISH, respectively. Of 113 patients with chromosomal abnormalities, 31 patients (27.4%) had hyperdiploid and 26 of 31 patients with hyperdiploidy had both numerical and structural anomalies. On the other hand, non-hyperdiploidy was observed in 62 patients (54.8%). The most common gains of chromosomes were 15, 9, 19 followed by 3, 5, 11, and 21. Whole chromosome losses were also frequent involving Y, 13 and 22 chromosomes. In our patients, 1q gain was determined in a total of 25 patients (22%), including 7 structural abnormalities and 19 unbalanced translocations causing complete or partial duplication of the long arm of chromosome 1. Although the breakpoints were different, t(1;5) balanced translocation and unbalanced translocations of t(1;2), t(1;3), t(1;7), t(1;16) and t(1;19) were observed twice. The most common structural abnormality was the deletion of the short arm of chromosome 13 (13q) or monosomy of chromosome 13 (-13) (24.1%, 61/253) in patients evaluated by FISH. Deletion involving chromosome 17p (del 17p) or monosomy of chromosome 17 (-17) were found in 31 (12.3%) patients. Translocations involving IgH regions were as follows: t(11;14)(q13;q32.33) in 22 (8.7%), t(4;14)(p16.3;q32.33) in 22 (8.7%) and t(14;16)(q32.33;q23.1) in 2 (0.8%) patients. In addition, t(14;17)(q32;q21) translocation was detected in a multiple myeloma patient for the first time in this study. There are a limited number of large study groups including both cytogenetic and FISH findings in MM patients. As the number of these studies increases, it is thought that new cytogenetic data can be guiding especially in clinical risk determination.

Dataset Information

Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma.

Publications

Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma.

Similar Datasets

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