Localization of Human Cadherin Genes to Chromosome Regions Exhibiting Cancer-Related Loss of Heterozygosity

Kremmidiotis, Gabriel; Baker, Elizabeth; Crawford, Joanna; Eyre, Helen J.; Nahmias, Joseph; Callen, David F.

doi:10.1006/geno.1998.5281

Cited by 70 publications

(44 citation statements)

References 23 publications

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“…CDH19 seems to be expressed in various tissues including some of epithelial origin (Kools et al, 2000). Localization of human cadherin genes has been related to regions exhibiting loss of heterozygosity as CDH16 at 8q22.1 in acute leukemia, CDH15 and CDH13 at 16q24.3 and 16q24 in breast cancer (Kremmidiotis et al, 1998). The finding that CDH19 maps 18q22 and could be down-regulated in head and neck cancer cell lines, needs to be further characterized by studying CDH19 expression in tumor and non tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma

et al. 2002

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The 18q chromosome arm is frequently lost in advanced head and neck squamous cell carcinoma. Twenty-four microsatellite markers located on chromosome 18q were genotyped in 145 primary tumors and 10 cell lines in order to identify putative tumor suppressor genes implicated in tumor progression. Two different minimal common regions of loss (MCRL) were identified at 18q22 and 18q23 respectively. To refine and delineate boundaries of an homozygous deletion found in one cell line, 44 extra markers located at 18q22 were analysed and the homozygous deletion was precisely defined within a critical region of 4.9 Mb. Four known genes (CDH7, CDH19, DNAM-1, FLJ23594) located in this critical region and two EST clusters (Hs.96900, Hs.98628) were selected for further investigations. For these six genes, genomic structures were established, somatic mutations were screened in 20 HNSCC and 10 cell lines and transcription levels were determined in eight cell lines. No somatic mutations were found in any of the candidate genes analysed (57 coding exons). However, differential transcription levels were observed for CDH19 and Hs.96900 in head and neck cancer cell lines supporting their putative involvement through down regulation mechanisms in head and neck cancer progression.

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Section: Discussionmentioning

confidence: 99%

Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma

et al. 2002

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“…There are no well-known tumor suppressor genes at these regions, but the cadherin 7 gene (CDH7), at 18q22.1, could be one candidate. 27 CDH7 has not been studied in cancers, but a mutation in the E-cadherin gene (CDH1) has been detected in ovarian carcinoma. 28 In a previous allelotype study of ovarian carcinoma, using six markers at 18q, the smallest region of overlap was also found distal to 18q21.…”

Section: Discussionmentioning

confidence: 99%

Allelic Analysis of Serous Ovarian Carcinoma Reveals Two Putative Tumor Suppressor Loci at 18q22-q23 Distal to SMAD4, SMAD2, and DCC

Lassus

Salovaara

Aaltonen

et al. 2001

The American Journal of Pathology

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The distal half of chromosome arm 18q is frequently lost in ovarian carcinoma. To define the putative tumor suppressor locus/loci more precisely we performed allelic analysis with 27 polymorphic microsatellite markers located at 18q12.3-q23 in 64 serous and 9 mucinous ovarian carcinomas. Fifty-nine percent of the serous carcinomas, but only one (11%) of mucinous carcinomas, showed allelic loss at one or more loci (P ‫؍‬ 0.018). In serous carcinomas, deletions were found to be associated with tumor grade and poor survival. The highest frequency of losses was detected at the distal part, 18q22-q23. Two minimal common regions of loss (MCRL) were identified at this region: MCRL1 between D18S465 and D18S61 at 18q22 (3.9 cM) and MCRL2 between D18S462 and D18S70 at 18q23 (5.8 cM). At 18q21.1, proximal to the MCRLs, there are three candidate tumor suppressor genes: SMAD4 (DPC4), SMAD2, and DCC. Their protein expression was studied by immunohistochemistry in normal ovarian tissue and serous carcinomas. Lost or very weak expression of SMAD4, SMAD2 and DCC was found in 28, 28, and 30% of serous carcinomas, respectively. Comparison of allelic loss and protein expression status indicated that none of these genes alone could be the target for the frequent allelic loss at 18q21.1. Together, these genes may account for a substantial proportion of the events, but not all of them. Thus, we propose that the frequent allelic loss at 18q is because of the effect of multiple genes, and there is at least one as yet unidentified tumor suppressor gene at 18q residing distal to SMAD4, SMAD2, and DCC involved in serous ovarian carcinoma. (Am J Pathol 2001, 159:35-42) On the basis of comparative genomic hybridization analyses, the distal half of 18q is a site of frequent loss of genetic material in ovarian carcinoma. 1,2 Three candidate tumor suppressor genes have been identified at 18q21.1: SMAD4 (DPC4), SMAD2, and DCC, 3-5 but few mutations in these genes have been detected in ovarian carcinoma. 6 -8 Ovarian carcinoma originates from the surface epithelium of the ovary. DCC has been shown to be expressed in the surface epithelium, 9 but it is not known if SMAD4 and SMAD2 are expressed in these cells. Furthermore, it is unknown if the expression of DCC, SMAD4, and SMAD2 is lost during malignant transformation. Previously, allelic loss has been studied with several markers at 18q21 in ovarian carcinoma, but fine allelotyping has not been performed at more distal regions of 18q (18q22-q23), which is the site of most frequent loss as suggested by comparative genomic hybridization results. 1,2 Ovarian carcinoma shows several different histological types, including serous, mucinous, endometrioid, and clear cell carcinomas. There is an increasing amount of biological and molecular evidence that different histological types of ovarian carcinoma should be regarded as distinct entities. 10 -14 The most common form of ovarian carcinoma is the serous histological type, which accounts for ϳ55% of all cases. In our previous comparative genomic hybri...

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“…22 A physical map covering the 16q22.1 region has been constructed 10 and the publication of the draft sequence of the human genome has facilitated the study of multiple genes located in its vicinity. The most obvious candidate TSGs in breast cancer at this region are, firstly, genes that are involved in cell-cell adhesion (members of the cadherin family) [E-cadherin (CDH1), 8,23,24 ], P-cadherin (CDH3), 25,26 VE-cadherin (CDH5) 27 and Ks-cadherin (CDH16) 28 ]; second, genes involved in cell cycle control and cell growth [E2F-transcription factor-4 (E2F-4) 29 and CTCF gene 30 ;] and, third, genes related to telomere function and hence cell senescence and cell immortality [Telomeric repeat binding factor-2 (TRF2) 31,32 ].…”

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confidence: 99%

High‐resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry

Rakha

Armour

Pinder

et al. 2005

Intl Journal of Cancer

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Loss of the chromosomal material at 16q22.1 is one of the most frequent genetic aberrations found in both lobular and low-grade nonlobular invasive carcinoma of the breast, indicating the presence of a tumour suppressor gene (TSG) at this region in these tumours. However, the TSG (s) at the 16q22.1 in the more frequent nonlobular carcinomas is still unknown. Multiplex Amplifiable Probe Hybridisation (MAPH) is a simple, accurate and a high-resolution technique that provides an alternative approach to DNA copy-number measurement. The aim of our study was to examine the most likely candidate genes at 16q22.1 using MAPH assay combined with protein expression analysis by immunohistochemistry. We identified deletion at 16q22.1 that involves some or all of these genes. We also noticed that the smallest region of deletion at 16q22.1 could be delineated to a 3 Mb region centromeric to the P-cadherin gene. Apart from the correlation between E-cadherin protein expression and its gene copy number, no correlation was detected between the expression of E2F-4, CTCF, TRF2 or P-cadherin with their gene's copy number. In the malignant tissues, no significant loss or decrease of protein expression of any gene other than E-cadherin was seen in association with any specific tumour type. No expression of VE-cadherin or Ksp-cadherin was detected in the normal and/or malignant tissues of the breast in these cases. However, there was a correlation between increased nuclear expression of E2F-4 and tumours with higher histological grade (p ‫؍‬ 0.04) and positive lymph node disease (p ‫؍‬ 0.02), suggesting that it may have an oncogenic rather than a tumour suppressor role. The malignant breast tissues also showed abnormal cytoplasmic cellular localisation of CTCF, compared to its expression in the normal parenchymal cells. In conclusion, we have demonstrated that MAPH is a potential technique for assessment of genomic imbalances in malignant tissues. Although our results support E-cadherin as the TSG in invasive lobular carcinoma, they argue against the candidacy of E2F-4, CTCF, TRF2, P-cadherin, Ksp-cadherin and VE-cadherin as TSGs in breast cancer.

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Localization of Human Cadherin Genes to Chromosome Regions Exhibiting Cancer-Related Loss of Heterozygosity

Cited by 70 publications

References 23 publications

Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma

Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma

Allelic Analysis of Serous Ovarian Carcinoma Reveals Two Putative Tumor Suppressor Loci at 18q22-q23 Distal to SMAD4, SMAD2, and DCC

High‐resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry

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