Possible roles for activating RAS mutations in the MGUS to MM transition and in the intramedullary to extramedullary transition in some plasma cell tumors.

Abstract:

:To assess a possible role in tumor progression, the occurrence and type of K- and N-RAS mutations were determined in purified tumor cells, including samples from patients with premalignant monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and extramedullary plasma cell (PC) tumors (ExPCTs). Immunophenotypic aberrant PCs were flow sorted from 20 MGUS, 58 MM, and 13 ExPCT patients. One RAS mutation was identified in 20 MGUS tumors (5%), in contrast to a much higher prevalence of RAS mutations in all stages of MM (about 31%). Further, oncogene analyses showed that RAS mutations are not evenly distributed among different molecular subclasses of MM, with the prevalence being increased in MM-expressing cyclin D1 (P = .015) and decreased in MM with t(4;14) (P = .055). We conclude that RAS mutations often provide a genetic marker if not a causal event in the evolution of MGUS to MM. Surprisingly, RAS mutations were absent in bone marrow tumor cells from all patients with ExPCT, a result significantly different from intramedullary MM (P = .001). From 3 of 6 patients with paired intramedullary and extramedullary PCs and identical immunoglobulin heavy chain gene (IgH) sequences, RAS mutations were identified only in extramedullary PCs, suggesting a role for RAS mutations in the transition from intramedullary to extramedullary tumor.

journal_name

Blood

journal_title

Blood

authors

Rasmussen T,Kuehl M,Lodahl M,Johnsen HE,Dahl IM

doi

10.1182/blood-2004-03-0833

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

317-23

issue

1

eissn

0006-4971

issn

1528-0020

pii

2004-03-0833

journal_volume

105

pub_type

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