Journal article
A multiple myeloma-specific capture sequencing platform discovers novel translocations and frequent, risk-associated point mutations in IGLL5
Blood cancer journal (New York), Vol.8(3), pp.35-10
03/21/2018
DOI: 10.1038/s41408-018-0062-y
PMCID: PMC5862875
PMID: 29563506
Abstract
Multiple myeloma (MM) is a disease of copy number variants (CNVs), chromosomal translocations, and single-nucleotide variants (SNVs). To enable integrative studies across these diverse mutation types, we developed a capture based sequencing platform to detect their occurrence in 465 genes altered in MM and used it to sequence 95 primary tumor-normal pairs to a mean depth of 104x. We detected cases of hyperdiploidy (23%), deletions of 1p (8%), 6q (21%), 8p (17%), 14q (16%), 16q (22%), and 17p (4%), and amplification of 1q (19%). We also detected IGH and MYC translocations near expected frequencies and non-silent SNVs in NRAS (24%), KRAS (21%), FAM46C (17%), TP53 (9%), DIS3 (9%), and BRAF (3%). We discovered frequent mutations in IGLL5 (18%) that were mutually exclusive of RAS mutations and associated with increased risk of disease progression (p = 0.03), suggesting that IGLL5 may be a stratifying biomarker. We identified novel IGLL5/IGH translocations in two samples. We subjected 15 of the pairs to ultra-deep sequencing (1259x) and found that although depth correlated with number of mutations detected (p = 0.001), depth past similar to 300x added little. The platform provides cost-effective genomic analysis for research and may be useful in individualizing treatment decisions in clinical settings.
Details
- Title: Subtitle
- A multiple myeloma-specific capture sequencing platform discovers novel translocations and frequent, risk-associated point mutations in IGLL5
- Creators
- Brian S. White - Washington University in St. LouisIrena Lanc - Washington University in St. LouisJulie O'Neal - Washington University in St. LouisHarshath Gupta - Washington University in St. LouisRobert S. Fulton - Washington University in St. LouisHeather Schmidt - Washington University in St. LouisCatrina Fronick - Washington University in St. LouisEdward A. Belter - Washington University in St. LouisMark Fiala - Washington University in St. LouisJustin King - Washington University in St. LouisGreg J. Ahmann - Division of Hematology-Oncology, Mayo Clinic, Rochester, 55905, MN, USA.Mary DeRome - Multiple Myeloma Research FoundationElaine R. Mardis - Nationwide Children's HospitalRavi Vij - Washington University in St. LouisJohn F. DiPersio - Washington University in St. LouisJoan Levy - Multiple Myeloma Research FoundationDaniel Auclair - Multiple Myeloma Research FoundationMichael H. Tomasson - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Blood cancer journal (New York), Vol.8(3), pp.35-10
- DOI
- 10.1038/s41408-018-0062-y
- PMID
- 29563506
- PMCID
- PMC5862875
- NLM abbreviation
- Blood Cancer J
- ISSN
- 2044-5385
- eISSN
- 2044-5385
- Publisher
- Springer Nature
- Number of pages
- 10
- Grant note
- P30 CA016058; P30 CA086862; U54 CA199092 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 03/21/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984359806202771
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