Details

Autor(en) / Beteiligte

• White, Brian S.
• Lanc, Irena
• O’Neal, Julie
• Gupta, Harshath
• Fulton, Robert S.
• Schmidt, Heather
• Fronick, Catrina
• Belter, Edward A.
• Fiala, Mark
• King, Justin
• Ahmann, Greg J.
• DeRome, Mary
• Mardis, Elaine R.
• Vij, Ravi
• DiPersio, John F.
• Levy, Joan
• Auclair, Daniel
• Tomasson, Michael H.

Titel

A multiple myeloma-specific capture sequencing platform discovers novel translocations and frequent, risk-associated point mutations in IGLL5

Ist Teil von

• Blood cancer journal (New York), 2018-03, Vol.8 (3), p.35-10, Article 35

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 104×. 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 (1259×) and found that although depth correlated with number of mutations detected ( p  = 0.001), depth past ~300× added little. The platform provides cost-effective genomic analysis for research and may be useful in individualizing treatment decisions in clinical settings.