Molecular analysis of chromosomh 1 abnormalities in human gliomas reveals frequent loss of 1p in oligodendroglial tumors

Abstract

Alterations of the short arm of chromosome I are recurrently found in cytogenetic analysis of malignant gliomas, and deletions of 1~3 6 .~3 2 region characterize at least the higher-grade tumors, glioblastorna multiforme. Molecular analysis of tumorderived and normal genomic DNA from 57 cases of gliomas, using a panel of chromosome I-specific DNA probes showed LOH in 16 tumors. Allelic losses on I p were primarily restricted to glioblastoma multiforme (2/ I I) and to tumors with a major oligodendroglial component: grade II oligodendrogliomas (6/6), grade 111 anaplastic oligodendrogliomas (5/6) and grade 11-111 mixed oligo-astrocytomas (2/3). Losses for Iq markers were detected in only I tumor (glioblastoma multiforme). Our data suggest that anomalies of I p primarily characterize oligodendrogliomas, whereas they are rare events in astrocytic tumors and indicate that a tumor-suppressor gene on I p36-p32 is involved in the development of brain tumors with oligodendroglial differentiation. Q 1994 Wiley-Liss, Inc.Gliomas represent about 5% of all adult human cancers and account for the vast majority of primary tumors of the central nervous system. They are classified histologically into lowgrade (grades I and 11) tumors, such as astrocytomas, oligodendrogliomas and ependymomas as well as some mixed forms (oligo-astrocytoma), and high-grade or malignant tumors

Clinical Categories of Neuroblastoma Are Associated with Different Patterns of Loss of Heterozygosity on Chromosome Arm 1p

“…For instance, several regions of chromosome 1p, including 1p36 and 1p22, have been implicated in the tumorigenesis of a wide range of malignancies. [37][38][39][40][41][42][43][44][45][46][47][48][49] Prior LOH studies in NB have used a variety of techniques and most have focused on 1p36. The incidence of 1p36 LOH in the literature ranges from 19 to 36%.…”

Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype

“…Numerous genetic alterations have been de®ned in human gliomas (Ransom et al, 1992;Bello et al, 1994Bello et al, , 1995Reifenberger et al, 1994;Kraus et al, 1995;Mohapatra et al, 1995Mohapatra et al, , 1998Louis and Gusella, 1995;Weber et al, 1996;Louis, 1997). Brie¯y, tumors of astrocytic lineage often demonstrate alterations of chromosome arms 7p, 7q, 9p, 10p, 10q, 11p, 13q, 17p, 19q and 22q, while oligodendrogliomas and MOAs commonly have loss of 1p and 19q.…”

“…All 40 gliomas with any evidence of imbalance on 1p included the D1S1612 to D1S468 region in the deletion. Bello et al (1994) placed the region of common loss on 1p in human gliomas in the interval spanning 1p32 ± p36. The present study narrows this region of common allelic loss to a segment within 1p36.…”

“…CGH data presented is that of chromosomes 1 and 19 only mas with alteration of 1p often lose the entire chromosome arm. Other investigators have also relied on high-grade astrocytomas to delineate 1p regions of overlapping deletion (Bello et al, 1994).…”

A new candidate site for a tumor suppressor gene involved in mouse thymic lymphomagenesis is located on the distal part of chromosome 4

“…This region is synthetic to that on human chromosome 1p34-36 (Mock et al, 1996), which is frequently deleted in di erent cancer types, such as breast tumors (Bieche et al, 1994), colon cancer (Bardi et al, 1993), germ cell cancer (Mathew et al, 1994), gliomas (Bello et al, 1994a), hepacellular carcinomas (Simon et al, 1991), leiomyosarcomas (Sreekantaiah et al, 1993), melanomas (Sokova et al, 1992), meningiomas (Bello et al, 1994b), neuroblastomas (Fong et al, 1992), pancreatic cancer (Ding et al, 1992), pheochromocytomas (Moley et al, 1992) and thyroid tumors (Khosla et al, 1991).…”