Regional assignment of the human loci for uvomorulin (UVO) and chymotrypsinogen B (CTRB) with the help of two overlapping deletions on the long arm of chromosome 16

Natt, Ernst; Magenis, R. Ellen; Zimmer, J.; Mansouri, Ahmed; Scherer, Gerd

doi:10.1159/000132745

Cited by 83 publications

(45 citation statements)

References 8 publications

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“…The human E-cadherin gene has been mapped to chromosome 16q22.1 (Mansouri et al, 1988;Natt et al, 1989). Its expression was reduced in several types of human carcinomas (Shimoyama et al, 1991;Bussemakers et al, 1992;Inoue et al, 1992;Umbas et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Chromosome alterations and E-cadherin gene mutations in human lobular breast cancer

et al. 1999

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We have studied a set of 40 human lobular breast cancers for loss of heterozygosity (LOH) at various chromosome locations and for mutations in the coding region plus flanking intron sequences of the E-cadherin gene. We found a high frequency of LOH (100%, 31/31) at 16q21–q22.1. A significantly higher level of LOH was detected in ductal breast tumours at chromosome arms 1p, 3p, 9p, 11q, 13q and 18q compared to lobular breast tumours. Furthermore, we found a significant association between LOH at 16 q containing the E-cadherin locus and lobular histological type. Six different somatic mutations were detected in the E-cadherin gene, of which three were insertions, two deletions and one splice site mutation. Mutations were found in combination with LOH of the wild type E-cadherin locus and loss of or reduced E-cadherin expression detected by immunohistochemistry. The mutations described here have not previously been reported. We compared LOH at different chromosome regions with E-cadherin gene mutations and found a significant association between LOH at 13 q and E-cadherin gene mutations. A significant association was also detected between LOH at 13q and LOH at 7q and 11q. Moreover, we found a significant association between LOH at 3 p and high S phase, LOH at 9p and low ER and PgR content, LOH at 17p and aneuploidy. We conclude that LOH at 16q is the most frequent chromosome alteration and E-cadherin is a typical tumour suppressor gene in lobular breast cancer. © 1999 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 99%

Chromosome alterations and E-cadherin gene mutations in human lobular breast cancer

et al. 1999

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“…These correl ative findings are highly suggestive of an important role of E-cadherin in preventing the transition to tumorous and/or invasive growth. Even more intriguing is the possibility that the human E-cadherin gene located at 16q22.1 (Natt et al, 1989) may correspond to a TSG identified by loss of heterozygosity in this genetic region in hepatocellular, breast, and prostate car cinomas (Carter et al, 1990;Sato et al, 1990;Tsuda et al, 1990;Zhang et al, 1990). If E-cadherin plays an important role in tumor suppression, the fa t locus may provide a useful model system for investigating the mechanism of this effect.…”

Section: Hyperplastic Overgrowth Mutants Fat: a Tsg Encoding A Putatimentioning

confidence: 99%

Drosophila in cancer research: the first fifty tumor suppressor genes

Watson

Justice

Bryant

1994

Journal of Cell Science

110

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SUMMARYIn Drosophila, over 50 genes have been identified in which loss-of-function mutations lead to excess cell proliferation in the embryo, in the central nervous system, imaginal discs or hematopoietic organs of the larva, or in the adult gonads. Twenty-two of these genes have been cloned and characterized at the molecular level, and nine of them show clear homology to mammalian genes. Most of these mammalian genes had not been previously implicated in cell proliferation control. Overgrowth in some of the mutants involves conversion to a cell type that, in normal development, shows more cell proliferation than the original cell type. Thus the neurogenic mutants, including Notch, show conversion of epidermal cells to neuroblasts, leading to the 'neurogenic' phenotype of excess nervous tissue. The ovarian tumor mutants show conversion of the female germ line to a cell type resembling the male germ line, which undergoes more proliferation than the female germ line. Mutations of the fa t locus cause hyperplastic overgrowth of imaginal discs, in which the epithelial structure is largely intact. The predicted fat protein product is a giant relative of cadherins, supporting indica tions from human cancer that cadherins play an important role in tumor suppression. Mutations in the lethal(2)giant larvae and lethal(l)discs large genes cause neoplastic over growth of imaginal discs as well as the larval brain. The dig gene encodes a membrane-associated guanylate kinase homolog that is localized at septate junctions between epithelial cells. This protein is a member of a family of homologs that also includes two proteins found at mammalian tight junctions (ZO-1 and ZO-2) and a protein found at mammalian synaptic junctions (PSD-95/SAP90). Genes in which mutations cause blood cell overproduction include aberrant immune response-8, which encodes the RpS6 ribosomal protein and hopscotch, which encodes a putative non-receptor protein tyrosine kinase. The gene products identified by ovarian tumor mutants do not show clear amino acid sequence homology to known proteins. Drosophila provides an opportunity to rapidly identify and characterize tumor suppressor genes, many of which have mammalian homologs that might also be involved in cell proliferation control and tumor suppression.

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“…1 E-cadherin was suggested to act as an invasion and metastasis suppressor since its loss in benign tumors could lead to a rapid progression into invasive, metastatic carcinomas. 2 CDH1 was mapped to the chromosome region 16q22.1, 3 which shows frequent allelic imbalance in a variety of tumors and is believed to harbor a tumor-suppressor gene. Mutation analysis of the coding region has been carried out in endometrial and ovarian carcinomas, 4 thyroid, 5 prostate, 6 bladder, 7 colorectal, 8 gastric, 9 breast 10 -14 and colon cancer, 15 but frequent CDH1 mutations were only found in diffuse gastric and infiltrative lobular breast carcinomas.…”

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confidence: 99%

CDH1 mutations are present in both ductal and lobular breast cancer, but promoter allelic variants show no detectable breast cancer risk

Lei

Sjöberg-Margolin²,

Salahshor

et al. 2001

Intl Journal of Cancer

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Mutations and diminished expression of the E-cadherin gene (CDH1) have been identified in a number of epithelial malignancies. Although somatic CDH1 mutations were detected in lobular breast cancer with a frequency ranging from 10 -56%, CDH1 alterations in more frequent ductal tumors appear to be rare. Here we have analyzed the coding region of CDH1 for mutations using denaturing high performance liquid chromatography and found 4 mutations in 83 ductal carcinomas (5%) and 3 mutations in 25 lobular carcinomas (12%). The germline of 13 patients with familial lobular tumors was also analyzed for mutations, but none were detected. In a case-control study, we also tested whether a variant adenine allele in the promoter polymorphism ؊161C3 A with a putative influence on the transcriptional activity of CDH1 in vitro confers any detectable risk of breast cancer. No significant difference in the allelic frequency between patients with breast cancer (326/1,152, 28.3%) and controls (190/696, 27.3%, p > 0.05; relative risk 1.05, 95% confidence interval 0.85-1.30) was found. A novel promoter polymorphism was identified at position ؊152, but the frequency of the variant cytosine allele was also similar in patients with breast cancer and controls (0.71% vs. 0.21%, p ‫؍‬ 0.23). Transient transfection experiments using reporter constructs containing the nucleotide substitutions ؊161C/ ؊152C and ؊161A/؊152T showed only a slight decrease in the transcription activity compared to the wild-type construct. These results do not support CDH1 as a prominent low-penetrance cancer susceptibility gene, but indicate that CDH1 mutations contribute to the progression of both lobular and ductal tumors. © 2002 Wiley-Liss, Inc. Key words: E-cadherin; mutation; breast cancer; promoter; SNPThe E-cadherin gene (CDH1, OMIM 192090) encodes an adhesion molecule important for establishing cell polarity and maintaining normal tissue morphology and cellular differentiation. 1 E-cadherin was suggested to act as an invasion and metastasis suppressor since its loss in benign tumors could lead to a rapid progression into invasive, metastatic carcinomas. 2 CDH1 was mapped to the chromosome region 16q22.1, 3 which shows frequent allelic imbalance in a variety of tumors and is believed to harbor a tumor-suppressor gene. Mutation analysis of the coding region has been carried out in endometrial and ovarian carcinomas, 4 thyroid, 5 prostate, 6 bladder, 7 colorectal, 8 gastric, 9 breast 10 -14 and colon cancer, 15 but frequent CDH1 mutations were only found in diffuse gastric and infiltrative lobular breast carcinomas. 10,11,16 Although ductal tumors are much more common than lobular breast cancer, CDH1 mutations have been observed in lobular carcinomas at a frequency exceeding 50%, 11 but were not found in ductal tumors in several studies, 10,11,16,17 suggesting a differential role for CDH1 in the development of the 2 malignancies. However, recent studies reported CDH1 alterations in cell lines derived from ductal tumors 18 and in a single case of ductal carcinom...

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Regional assignment of the human loci for uvomorulin (UVO) and chymotrypsinogen B (CTRB) with the help of two overlapping deletions on the long arm of chromosome 16

Cited by 83 publications

References 8 publications

Chromosome alterations and E-cadherin gene mutations in human lobular breast cancer

Chromosome alterations and E-cadherin gene mutations in human lobular breast cancer

Drosophila in cancer research: the first fifty tumor suppressor genes

CDH1 mutations are present in both ductal and lobular breast cancer, but promoter allelic variants show no detectable breast cancer risk

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