Expression of cellular adhesion molecule ‘OPCML’ is down‐regulated in gliomas and other brain tumours

Abstract

The four GPI-anchored cell adhesion molecules that exemplify the IgLON family are most highly expressed in the nervous system and associate to form up to six different heterodimeric 'Diglons' that can modify cell adhesion and inhibit axon migration. Recently, two members, OPCML and LSAMP, were identified as putative tumour suppressor genes in ovarian and renal carcinomas respectively. In this study, we investigated OPCML expression in nonneoplastic brain tissue and 35 brain tumours (18 glioblastoma multiformes, five anaplastic gliomas, five meningiomas, six metastases and one medulloblastoma) and four glioma cell lines using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). OPCML was highly expressed in cerebellum, less so in cerebral cortex, frontal lobe and meninges and was significantly reduced or absent in 83% of brain tumours and all cell lines compared with nonneoplastic whole brain. Two OPCML splice variants have been identified in humans, termed alpha1 and alpha2, but the latter has not been demonstrated in human neural tissues. Using PCR with specific primers, nonneoplastic brain and 3/6 of tested brain tumours expressed both splice variants, whereas the remaining brain tumours only expressed the alpha2 variant. Hypermethylation of the alpha1 OPCML promoter, associated with down-regulation of expression in ovarian tumours, did not correlate with expression levels in the subset of brain tumours tested, implying transcription of OPCML from an alternative promoter or a different mechanism of down-regulation. This study demonstrates that OPCML down-regulation occurs in the majority of brain tumours tested, warranting further investigation of OPCML and other IgLONs in the development and progression of brain tumours.

Evaluation of risk loci for schizophrenia derived from genome-wide association studies in a German population

“…The marker rs3016384 at chromosome 11q25 is located within OPCML which encodes for opioid binding protein/cell adhesion molecule like, a member of the immunoglobulin (Ig) domaincontaining superfamily (IgLON) and is found to be a tumor suppressor gene for multiple carcinomas and lymphomas due to promoter CpG methylation [Sellar et al, 2003;Reed et al, 2007;Cui et al, 2008]. The OPCML locus also appeared with suggestive evidence for linkage in an extended Dutch pedigree with late-onset Alzheimer's disease [Liu et al, 2007].…”

High-resolution genomic profiling of adult and pediatric core-binding factor acute myeloid leukemia reveals new recurrent genomic alterations

“…Moreover, LSAMP is contained within each of the other larger relapseassociated deletions. LSAMP has previously been reported to be frequently deleted, down-regulated, or epigenetically silenced in osteosarcoma, brain tumors, and renal cell carcinoma [34][35][36] ; however, to date no association of this lesions with relapsed AML has been reported.…”

Recurrent Focal Copy-Number Changes and Loss of Heterozygosity Implicate Two Noncoding RNAs and One Tumor Suppressor Gene at Chromosome 3q13.31 in Osteosarcoma

“…Whereas some of these CN changes may represent germline CNVs, most do not (Supplementary Table S6) as they are far more common than osteo3q13.31 CNVs, estimated to be present in <0.1% of healthy controls (41). LSAMP and a related gene have been implicated as TS in clear cell renal cell carcinoma (36), ovarian carcinoma (37), and glioma (38). During the preparation of this article, two groups (24,25) reported deletions at osteo3q13.31 in osteosarcoma, implicating LSAMP as an osteosarcoma TS.…”