Identification of two contiguous minimally deleted regions on chromosome 1p36.31–p36.32 in oligodendroglial tumours

Abstract

Loss of the short arm of chromosome 1 is a hallmark of oligodendroglial tumours (OTs). Deletion mapping studies in OTs have revealed multiple commonly deleted regions on chromosome 1p, suggesting that there are more than one tumour suppressor gene. To map critical deletion regions on 1p, a series of 25 OTs were examined for loss of heterozygosity (LOH) on 19 polymorphic markers across the 1p arm using microsatellite analysis. Our study revealed that 60% of tumours had LOH of all informative markers on 1p and identified one tumour showing LOH at telomeric markers only. Since this deletion region lies in one of the critical deletion intervals defined previously, we then screened another series of 27 OTs specifically at 1p36.3 for LOH using nine polymorphic markers. A total of 12% (six out of 52) of tumours were found to carry interstitial deletions. The allelic status and the deletion breakpoints in these tumours with interstitial deletion were further verified by fluorescent in situ hybridisation. The small overlapping intervals facilitated the delineation of two contiguous minimally deleted regions of 0.76 Mb, defined by D1S468 and D1S2845, and of 0.41 Mb, bound by D1S2893 and D1S1608, on 1p36.31 -36.32. Based on current reference human genome sequence these deletion regions have been sequenced almost to entirety and contain eight annotated genes. TP73, DFFB and SHREW1 are the only known genes located in these deletion regions, while the others are uncharacterised novel genes. In conclusion, our study has narrowed down the critical tumour suppressor loci on 1p36.3, in which two minimally deleted regions are mapped, and markedly reduced the number of candidate genes to be screened for their involvement in OT development.

The SHREW1 gene, frequently deleted in oligodendrogliomas, functions to inhibit cell adhesion and migration

“…14 It should be noted that during the course of our study, a nearly identical consensus region of deletion was identified in an independent study of 52 oligodendroglial tumors, with SHREW1 as the only gene in the consensus region. 15 SHREW1 encodes a novel transmembrane protein in adherens junctions. 16 The loss of adherens junctions has been shown to promote tumor cell infiltration and metastasis.…”

TERT promoter mutations contribute to subset prognostication of lower-grade gliomas

“…20 In brief, 5-mm thick formalin-fixed, paraffin-embedded sections were deparaffinized in xylene, treated with 1 M sodium thiocyanate at 80 1C for 10 min, digested in pepsin solution at 37 1C for 20-30 min, rinsed in milli-Q water and dehydrated. Locus-specific probes were generated from bacterial artificial chromosome clones using nick translation, in the presence of Spectrum Orange deoxyuridine triphosphate (dUTP) …”

Tiny Actors, Great Roles: microRNAs in p53's Service

“…In line with this conjecture, the genomic region 1p36, encompassing the miR-34a gene, is frequently deleted in a variety of human cancers. 48,53,54 Welch et al reported that the miRNA-34a gene is hemizygously deleted in approximately 30% of advanced stage neuroblastomas and that mature miR-34a is under-expressed in primary neuroblastoma tumors and cell lines. 48 Furthermore, ectopic overexpression of miR-34a induced growth arrest and apoptosis in neuroblastoma-derived cells.…”