Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population
<p>Abstract</p> <p>The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (<it>APC</it>) and <it>β-catenin </it>plays an important role in transfor...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-07-01
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| Series: | Human Genomics |
| Subjects: | |
| Online Access: | http://www.humgenomics.com/content/5/5/441 |
| _version_ | 1798038371435544576 |
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| author | Sameer A Shah Zaffar A Abdullah Safiya Chowdri Nissar A Siddiqi Mushtaq A |
| author_facet | Sameer A Shah Zaffar A Abdullah Safiya Chowdri Nissar A Siddiqi Mushtaq A |
| author_sort | Sameer A |
| collection | DOAJ |
| description | <p>Abstract</p> <p>The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (<it>APC</it>) and <it>β-catenin </it>plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the <it>APC </it>and <it>β-catenin </it>genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR) of the <it>APC </it>gene and exon 3 of the β-<it>catenin </it>gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the <it>APC </it>gene was also carried out using methylation-specific PCR (MS-PCR). The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86). Promoter hypermethylation of <it>APC </it>was observed in 54.65 per cent (47 of 86) of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the <it>APC </it>gene (<it>p </it>≤ 0.05). Although the number of mutations in the <it>APC </it>and <it>β-catenin </it>genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, <it>APC</it>, of the Wnt pathway in the development of CRC in the Kashmiri population.</p> |
| first_indexed | 2024-04-11T21:39:17Z |
| format | Article |
| id | doaj.art-4c48f33dc5f84d1a962f5e2f4e2b2a4f |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-11T21:39:17Z |
| publishDate | 2011-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-4c48f33dc5f84d1a962f5e2f4e2b2a4f2022-12-22T04:01:39ZengBMCHuman Genomics1479-73642011-07-015544145210.1186/1479-7364-5-5-441Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri populationSameer AShah Zaffar AAbdullah SafiyaChowdri Nissar ASiddiqi Mushtaq A<p>Abstract</p> <p>The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (<it>APC</it>) and <it>β-catenin </it>plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the <it>APC </it>and <it>β-catenin </it>genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR) of the <it>APC </it>gene and exon 3 of the β-<it>catenin </it>gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the <it>APC </it>gene was also carried out using methylation-specific PCR (MS-PCR). The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86). Promoter hypermethylation of <it>APC </it>was observed in 54.65 per cent (47 of 86) of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the <it>APC </it>gene (<it>p </it>≤ 0.05). Although the number of mutations in the <it>APC </it>and <it>β-catenin </it>genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, <it>APC</it>, of the Wnt pathway in the development of CRC in the Kashmiri population.</p>http://www.humgenomics.com/content/5/5/441Wnt pathwayAPCβ-catenincolorectal cancerKashmirhypermethylationmutationsDukes' stage |
| spellingShingle | Sameer A Shah Zaffar A Abdullah Safiya Chowdri Nissar A Siddiqi Mushtaq A Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population Human Genomics Wnt pathway APC β-catenin colorectal cancer Kashmir hypermethylation mutations Dukes' stage |
| title | Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population |
| title_full | Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population |
| title_fullStr | Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population |
| title_full_unstemmed | Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population |
| title_short | Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population |
| title_sort | analysis of molecular aberrations of wnt pathway gladiators in colorectal cancer in the kashmiri population |
| topic | Wnt pathway APC β-catenin colorectal cancer Kashmir hypermethylation mutations Dukes' stage |
| url | http://www.humgenomics.com/content/5/5/441 |
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