Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker

被引：52

作者：

Chavan, S. S. ^{[1
]}

He, J. ^{[2
]}

Tytarenko, R. ^{[1
]}

Deshpande, S. ^{[1
]}

Patel, P. ^{[1
]}

Bailey, M. ^{[2
]}

Stein, C. K. ^{[1
]}

Stephens, O. ^{[1
]}

Weinhold, N. ^{[1
]}

Petty, N. ^{[1
]}

Steward, D. ^{[1
]}

Rasche, L. ^{[1
]}

Bauer, M. ^{[1
]}

Ashby, C. ^{[1
]}

Peterson, E. ^{[1
]}

Ali, S. ^{[2
]}

Ross, J. ^{[2
,3
]}

Miller, V. A. ^{[2
]}

Stephens, P. ^{[2
]}

Thanendrarajan, S. ^{[1
]}

Schinke, C. ^{[1
]}

Zangari, M. ^{[1
]}

van Rhee, F. ^{[1
]}

Barlogie, B. ^{[1
,4
]}

Mughal, T. I. ^{[2
,5
]}

Davies, F. E. ^{[1
]}

Morgan, G. J. ^{[1
]}

Walker, B. A. ^{[1
]}

机构：

[1] Univ Arkansas Med Sci, Myeloma Inst, 4301W Markham,816, Little Rock, AR 72205 USA

[2] Fdn Med Inc, Cambridge, MA USA

[3] Albany Med Coll, Albany, NY USA

[4] Icahn Sch Med, New York, NY USA

[5] Tufts Univ, Med Ctr, Boston, MA USA

来源：

BLOOD CANCER JOURNAL | 2017年 / 7卷

基金：

美国国家卫生研究院;

关键词：

POOR-PROGNOSIS; MOLECULAR CLASSIFICATION; EXPRESSION; DELETIONS; GENES; ABNORMALITIES; TRANSLOCATIONS; PATHOGENESIS; DEL(17P); SURVIVAL;

D O I：

10.1038/bcj.2017.12

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.

引用

页码：e535 / e535

页数：7

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