Identification and Characterization of a Novel Gene, C13orf25 , as a Target for 13q31-q32 Amplification in Malignant Lymphoma

Abstract

The amplification at 13q31-q32 has been reported in not only hematopoietic malignancies but also in other solid tumors. We identified previously frequent amplification of chromosomal band 13q31-q32 in 70 cases of diffuse large B-cell lymphoma patients by conventional comparative genomic hybridization analysis. In an attempt to identify a candidate gene within this region, we used array comparative genomic hybridization and fluorescent in situ hybridization to map the 13q31-q32 amplicon. We then screened the 65 expressed sequence tags and Glypican 5 (GPC5) by reverse transcription-PCR and Northern blotting. As a result, we identified a novel gene, designated Chromosome 13 open reading frame 25 (C13orf25), which was overexpressed in B-cell lymphoma cell lines and diffuse large B-cell lymphoma patients with 13q31-q32 amplifications. However, GPC5, which has been reported to be a target gene for 13q31-q32 amplification, was truncated in one cell line, Rec1, possessing the amplification, and its expression in various cell lines with amplification at 13q31-q32 was not significantly different from that in other cell lines without amplification, suggesting that GPC5 is not likely to be the candidate gene. Additional analysis identified two major transcripts in the C13orf25 gene. The two transcripts A and B predicted open reading frames of 32 and 70-amino acid polypeptides, respectively. The former has been reported as bA121J7.2, which is conserved among species. Transcript-B also contained seven mature microRNAs in its untranslated region. These results suggest that the C13orf25 gene is the most likely candidate gene for the 13q31-q32 amplicon found in hematopoietic malignancies.

Loss of chromosomes is the primary event in near-haploid and low-hypodiploid acute lymphoblastic leukemia

“…Of these, only MIR17HG has been previously associated with tumorigenesis; it is included in the 13q31 5 amplicon in lymphoma. 13 The only microdeletions identified in this study resulted in loss of CDKN2A in four cases and ETV6 in one case (Supplementary Table 1), corresponding to a mean of 0.42 microdeletions per case. This is a relatively low frequency compared with other subtypes of BCP ALL 14 and could be due to the fact that the leukemic cell has already lost massive amounts of genetic material; additional deletions may therefore not be necessary for leukemogenesis or be incompatible with cell viability.…”

Transcription factor C/EBP-β induces tumor-suppressor phosphatase PHLPP2 through repression of the miR-17–92 cluster in differentiating AML cells

“…The miR-17-92 cluster is frequently amplified in several lymphomas and in lung cancer, 16,42 and aberrant overexpression of the miR-17-92 polycistron is detected in many cancers. 43 Retinoblastoma-like 2 protein (p130, Rbl2), Cdk inhibitor p21CIP1, transforming growth factor β1 (TGFβ1), proapoptotic Bcl-2 protein Bim, the tumor-suppressor PTEN and transcription factor E2F1 are some of the cluster's targets.…”

MicroRNAs in cell proliferation, cell death, and tumorigenesis

“…The most comprehensively studied example of an miRNA locus with these properties is the mir-17 cluster, consisting of six miRNAs: miRs- 17-5p, -18, -19a, -19b, -20, and -92. This miRNA cluster is located on human chromosome 13q31, a region that is frequently amplified in several types of lymphoma and solid tumours (Ota et al, 2004). In a recent study, He et al (2005) found that miRNAs from this cluster are highly expressed in B-cell lymphoma samples and cell lines.…”