Transcriptional dysregulation of the deleted in colorectal carcinoma gene in multiple myeloma and monoclonal gammopathy of undetermined significance. Issue 12 (22nd September 2015)

• Record Type: Journal Article
• Authors: Nagoshi, Hisao; Taki, Tomohiko; Chinen, Yoshiaki; Tatekawa, Shotaro; Tsukamoto, Taku; Maegawa, Saori; Yamamoto‐Sugitani, Mio; Tsutsumi, Yasuhiko; Kobayashi, Tsutomu; Matsumoto, Yosuke; Horiike, Shigeo; Okuno, Yutaka; Fujiwara, Shiho; Hata, Hiroyuki; Kuroda, Junya; Taniwaki, Masafumi
• Is Part Of: Genes, chromosomes & cancer. Volume 54:Issue 12(2015:Dec.)
• Page Start: 788
• Page End: 795
• Publication Date: 2015-09-22
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22290
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The deleted in colorectal carcinoma <italic>(DCC)</italic> gene at 18q21 encodes a netrin‐1 receptor, a tumor suppressor that prevents cell growth. While allele loss or decreased expression of <italic>DCC</italic> 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 <italic>DCC</italic> transcriptional variants, in which exon 2 fuses with intron 1 instead of exon 1 (<italic>mt.DCC</italic>). Among them, two co‐expressed wild type transcripts (<italic>wt.DCC</italic>), while eight co‐expressed the splicing variant (<italic>sv.DCC</italic>) lacking exon 1. The remaining HMCL expressed only <italic>sv.DCC</italic>. In addition, analyses revealed that there were two types of <italic>mt.DCC</italic> 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, <italic>wt.DCC</italic> was expressed in 53% of MM, but not in MGUS, while 23% of MM and 75% of MGUS expressed only <italic>sv.DCC</italic>. Considering that 25% of MGUS, 57% of MM, and 91% HMCLs expressed <italic>mt.DCC</italic>, our results suggest that the acquisition of <italic>mt.DCC</italic> might be a secondary genetic change in plasma cell dyscrasia. © 2015 Wiley Periodicals, Inc.</p> </abstract>