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Transcriptional dysregulation of the deleted in colorectal carcinoma gene in multiple myeloma and monoclonal gammopathy of undetermined significance
Author(s) -
Nagoshi Hisao,
Taki Tomohiko,
Chinen Yoshiaki,
Tatekawa Shotaro,
Tsukamoto Taku,
Maegawa Saori,
YamamotoSugitani Mio,
Tsutsumi Yasuhiko,
Kobayashi Tsutomu,
Matsumoto Yosuke,
Horiike Shigeo,
Okuno Yutaka,
Fujiwara Shiho,
Hata Hiroyuki,
Kuroda Junya,
Taniwaki Masafumi
Publication year - 2015
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22290
Subject(s) - deleted in colorectal cancer , monoclonal gammopathy of undetermined significance , plasma cell dyscrasia , exon , multiple myeloma , cancer research , biology , intron , tumor suppressor gene , microbiology and biotechnology , gene , monoclonal , monoclonal antibody , colorectal cancer , cancer , immunology , carcinogenesis , genetics , antibody , immunoglobulin light chain
The deleted in colorectal carcinoma (DCC) gene at 18q21 encodes a netrin‐1 receptor, a tumor suppressor that prevents cell growth. While allele loss or decreased expression of DCC has been associated with the progression of solid tumors and hematologic malignancies, including leukemias and malignant lymphomas, its involvement has not been evaluated in multiple myeloma (MM), a plasma cell malignancy characterized by complex and heterogenous molecular abnormalities. We here show that 10 of 11 human myeloma‐derived cell lines (HMCLs) expressed non‐translated aberrant DCC transcriptional variants, in which exon 2 fuses with intron 1 instead of exon 1 ( mt.DCC ). Among them, two co‐expressed wild type transcripts ( wt.DCC ), while eight co‐expressed the splicing variant ( sv.DCC ) lacking exon 1. The remaining HMCL expressed only sv.DCC . In addition, analyses revealed that there were two types of mt.DCC that differed in their fusion of intron 1 with exon 2. In patient‐derived samples from 30 MM and 8 monoclonal gammopathy of undetermined significance (MGUS) patients, wt.DCC was expressed in 53% of MM, but not in MGUS, while 23% of MM and 75% of MGUS expressed only sv.DCC . Considering that 25% of MGUS, 57% of MM, and 91% HMCLs expressed mt.DCC , our results suggest that the acquisition of mt.DCC might be a secondary genetic change in plasma cell dyscrasia. © 2015 Wiley Periodicals, Inc.