Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Distal alterations of the short arm of chromosome 1 are among the most frequent cytogenetic abnormalities in human breast carcinoma. We studied 96 primary human breast carcinomas for allelic imbalance using a panel of 31 polymorphic microsatellite, restriction fragment length polymorphism, and variable number of tandem repeat markers located mainly in the 1p32-pter region. Allelic imbalance at one or more loci was observed on the short arm of chromosome 1 in 56 (58.3%) of the 96 tumors. The 56 1p-altered tumor DNAs showed loss of heterozygosity (LOH), 12 (21.4%) at all informative loci tested and 44 (78.6%) at some loci. The LOH pattern of these 44 partially deleted tumors identified two distinct consensus regions of deletion on 1p32-pter (1p36.3 and 1p32). These regions match those described by other investigators but are considerably smaller. The 1p32 band is located within one of the two 1p regions of LOH in neuroblastoma, suggesting the involvement of the same unidentified tumor suppressor gene in both human breast cancer and neuroblastoma. The candidate tumor suppressor genes TNFR2, RIZ, DAN, RAP1GA1, FGR, MDGI, EXTL, and hRAD54 were excluded from the two consensus regions of deletion identified at 1p32-pter. Analysis of six polymorphic markers chosen to map within the other deleted regions described in breast tumors confirmed that two additional breast tumor suppressor genes are located in the proximal part (1p22 and 1p13) of chromosome arm 1p. Taken together, these results suggest that several unknown suppressor genes on 1p might be involved in the development of breast cancer. The refinement of the regions of LOH to within a few cM, and the recent publication of transcript maps of the human genome, mean that candidate genes and expressed sequence tags mapping to these deleted regions can now be investigated.
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PMID:Deletion mapping of chromosomal region 1p32-pter in primary breast cancer. 1045 6

Recently, the EXTL1 gene, a member of the EXT tumor suppressor gene family, has been mapped to 1p36, a chromosome region which is frequently implicated in a wide variety of malignancies, including breast carcinoma, colorectal cancer and neuroblastoma. In this study, we show that the EXTL1 gene is located between the genetic markers D1S511 and D1S234 within 200 kb of the LAP18 gene on chromosome 1p36. 1, a region which has been proposed to harbor a tumor suppressor gene implicated in MYCN-amplified neuroblastomas. In addition, we determined the genomic structure of the EXTL1 gene, revealing that the EXTL1 coding sequence spans 11 exons within a 50-kb region.
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PMID:Refined physical mapping and genomic structure of the EXTL1 gene. 1057 24

Common genetic aberrations of neuroblastoma are deletions of the short arm of chromosome 1 (1p36) and MYCN amplification. Our deletion analysis of 25 tumor cell lines and 171 tumors strongly suggests that 1p harbors several tumor suppressor loci. Distinct loci are involved in MYCN single-copy versus MYCN-amplified neuroblastoma. Deletions in MYCN single-copy tumors have a shortest region of overlap (SRO) of 20 cM at 1p36.3. MYCN-amplified tumors have large deletions with an SRO of about 60 cM, from 1p36.1 to the telomere. This SRO is defined by D1S7 (1p36.1), which was the most distal locus retained. Therefore, a suppressor gene associated with MYCN-amplified tumors probably maps within a few megabases distal of D1S7. In order to map this locus, we further refined this SRO. We mapped the breakpoint of the MYCN-amplified neuroblastoma with the smallest 1p deletion between 56.6 and 57.2 cM from 1pter. Pulsed-field gel electrophoresis and radiation hybrid mapping were used to construct a 5-Mb physical map of this region. The map includes the region from 82.73 till 92.89 cR from 1pter. About half of it was isolated in P1 and PAC clones. The region harbors the genes FGR, SLC9A1, HMG17, EXTL1, AML2, RH, OP18, four ESTs, and a newly identified gene with a transcript size of approximately 7 Kb. Several of the mapped genes have a putative role in cell growth, differentiation, and morphogenesis. Genes Chromosomes Cancer 27:143-152, 2000.
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PMID:An integrated 5-Mb physical, genetic, and radiation hybrid map of a 1p36.1 region implicated in neuroblastoma pathogenesis. 1061 2

Although neuroblastoma is the most common extracranial solid tumour of childhood, little is known about its aetiology. Together with MYCN amplification and chromosome 17q gain, chromosome 1p deletion is one of the most frequently occurring genetic abnormalities in neuroblastoma. Based upon mapping of deletion breakpoints, putative tumour suppressor gene loci have been assigned to the distal part of the short arm of chromosome 1. Recently, the EXTL1 gene was suggested as a candidate neuroblastoma-suppressor gene and to evaluate this hypothesis, we performed 1p deletion analysis and mutation screening of the EXTL1-coding region on DNA from 22 primary neuroblastomas and 21 neuroblastoma cell lines. Deletions of the chromosome region 1p36.1, including the EXTL1 gene, were detected in several neuroblastoma cell lines and primary tumours. EXTL1 mutation screening resulted in the detection of one unclassified variant (Ser28Cys) but could not provide additional evidence of EXTL1 being involved in the aetiology of neuroblastoma.
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PMID:Molecular analysis of the putative tumour-suppressor gene EXTL1 in neuroblastoma patients and cell lines. 1511 Aug 91