Narrowing of the regions of allelic losses of chromosome 1p36 in meningioma tissues by an improved SSCP analysis

Abstract

Mapping loss of heterozygosity (LOH) regions in the genomes of tumor tissues is a practical approach for identifying genes whose loss is related to tumorigenesis. Conventional LOH analyses using microsatellite or single nucleotide polymorphism (SNP) markers require the simultaneous examination of tumor-and matched normal-DNA. Here, we improved the previously developed SNP-based LOH assay using single strand conformation polymorphism (SSCP) analysis, so that LOH in tumor samples heavily contaminated with normal DNA can now be precisely estimated, even when matched normal DNA is not available. We demonstrate the reliability of the improved SSCP-based LOH detection method, called the LOH estimation by quantitative SSCP analysis using averaged control (LOQUS-AC), by comparing the results with those of the previous ''LOH estimated by quantitative SSCP assay'' (LOQUS) method. Using the LOQUS-AC assay, LOH was detected at a high consistency (98.1%) with the previous LOQUS method. We then applied this new method to characterize LOH profiles in 130 meningiomas, using 68 SNPs (i.e., a mean inter-SNP interval of 441 kbp) that are evenly distributed throughout chromosome 1p36. Benign, atypical and anaplastic meningiomas exhibited 1p36 LOH at frequencies of 48.39, 84.62 and 100.00%, respectively, using LOQUS-AC. Subsequently, we detected a candidate common LOH region on 1p36.11 that might harbor tumor suppressor genes related to malignant progression of meningioma. ' 2007 Wiley-Liss, Inc.

Delineation of commonly deleted chromosomal regions in meningiomas by high‐density single nucleotide polymorphism genotyping arrays

“…In line with previous observations, 1p, 6q, 7p, and 14 were more frequently altered in these cases (Henn et al, 2003;Guan et al, 2008). Remarkably, the regions deleted in common at 6q and 7p are also shared by other malignant tumors (Trost et al, 2007;Klatte et al, 2009).…”

“…Early reports showed that monosomy 22/22qÀ is by far the most common cytogenetic alteration of meningiomas and that complex karyotypes, associated or not with monosomy 22/del(22q), are rare. Among other abnormalities, deletion of chromosome arms 1p and 6q as well as monosomy 14 and/or losses of the sex chromosomes are much more frequent than both chromosomal gains and tetraploidy (Simon et al, 2007;Guan et al, 2008) as confirmed by more sensitive techniques such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) arrays (Buckley et al, 2002). Altogether, these findings support the notion that monosomy 22 or del(22q) in association with mutation of the NF2 gene is the most frequent abnormality involved in meningiomas while del(1p) and monosomy 14 are the most informative alterations to predict recurrence (Maillo et al, 2007;Nakane et al, 2007;Ketter et al, 2008).…”

The molecular pattern of histopathological progression to anaplastic meningioma – A case report

“…The genetic profile of the tumour during the second surgery has not changed, but the tumour progressed histologically (Table 1). The risk of death in 2 years from diagnosis is greatly increased if a malignant tumour is diagnosed [2,11,12]. The sentence is not clear for me.…”

Persistent ER stress causes GPI anchor deficit to convert a GPI-anchored prion protein into pro-PrP via the ATF6–miR449c-5p–PIGV axis

“…The exact mechanism warrants further investigation. Losses of chromosome 1p36 in which the PIGV gene is located have been linked to a broad range of human malignancies ( 50 , 51 , 52 , 53 ). It is conceivable that loss of PIGV-induced pro-PrP may contribute to the progression of the malignant tumors.…”