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Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities
Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990292/ https://www.ncbi.nlm.nih.gov/pubmed/27430658 http://dx.doi.org/10.3892/ijmm.2016.2666 |
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author | Silva, Patrícia Albuquerque, Cristina Lage, Pedro Fontes, Vanessa Fonseca, Ricardo Vitoriano, Inês Filipe, Bruno Rodrigues, Paula Moita, Susana Ferreira, Sara Sousa, Rita Claro, Isabel Leitão, Carlos Nobre Chaves, Paula Pereira, António Dias |
author_facet | Silva, Patrícia Albuquerque, Cristina Lage, Pedro Fontes, Vanessa Fonseca, Ricardo Vitoriano, Inês Filipe, Bruno Rodrigues, Paula Moita, Susana Ferreira, Sara Sousa, Rita Claro, Isabel Leitão, Carlos Nobre Chaves, Paula Pereira, António Dias |
author_sort | Silva, Patrícia |
collection | PubMed |
description | Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and/or polyps/CRC (SPP-FHP/CRC). Sixty-two lesions from 12 patients with SPP-FHP/CRC and 6 patients with sporadic SPP were included. The patients with SPP-FHP/CRC presented with an older mean age at diagnosis (p=0.027) and a more heterogeneous histological pattern of lesions (p=0.032) than the patients with sporadic SPP. We identified two molecular forms of SPP-FHP/CRC, according to the preferential location of the lesions: proximal/whole-colon or distal colon. Mismatch repair (MMR) gene methylation [mutS homolog 6 (MSH6)/mutS homolog 3 (MSH3)] or loss of heterozygosity (LOH) of D2S123 (flanking MSH6) were detected exclusively in the former (p=3.0×10(−7)), in most early lesions. Proximal/whole-colon SPP-FHP/CRC presented a higher frequency of O-6-methylguanine-DNA methyltransferase (MGMT) methylation/LOH, microsatel-lite instability (MSI) and Wnt mutations (19/29 vs. 7/17; 16/23 vs. 1/14, p=2.2×10(−4); 15/26 vs. 2/15, p=0.006; 14/26 vs. 4/20, p=0.02) but a lower frequency of B-raf proto-oncogene, serine/threonine kinase (BRAF) mutations (7/30 vs. 12/20, p=0.0089) than the distal form. CRC was more frequent in cases of Kirsten rat sarcoma viral oncogene homolog (KRAS)-associated proximal/whole-colon SPP-FHP/CRC than in the remaining cases (4/4 vs. 1/8, p=0.01). Thus, SPP-FHP/CRC appears to be a specific entity, presenting two forms, proximal/whole-colon and distal, which differ in the underlying tumor initiation pathways. Early MGMT and MMR gene deficiency in the former may underlie an inherited susceptibility to genotoxic stress. |
format | Online Article Text |
id | pubmed-4990292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-49902922016-08-26 Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities Silva, Patrícia Albuquerque, Cristina Lage, Pedro Fontes, Vanessa Fonseca, Ricardo Vitoriano, Inês Filipe, Bruno Rodrigues, Paula Moita, Susana Ferreira, Sara Sousa, Rita Claro, Isabel Leitão, Carlos Nobre Chaves, Paula Pereira, António Dias Int J Mol Med Articles Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and/or polyps/CRC (SPP-FHP/CRC). Sixty-two lesions from 12 patients with SPP-FHP/CRC and 6 patients with sporadic SPP were included. The patients with SPP-FHP/CRC presented with an older mean age at diagnosis (p=0.027) and a more heterogeneous histological pattern of lesions (p=0.032) than the patients with sporadic SPP. We identified two molecular forms of SPP-FHP/CRC, according to the preferential location of the lesions: proximal/whole-colon or distal colon. Mismatch repair (MMR) gene methylation [mutS homolog 6 (MSH6)/mutS homolog 3 (MSH3)] or loss of heterozygosity (LOH) of D2S123 (flanking MSH6) were detected exclusively in the former (p=3.0×10(−7)), in most early lesions. Proximal/whole-colon SPP-FHP/CRC presented a higher frequency of O-6-methylguanine-DNA methyltransferase (MGMT) methylation/LOH, microsatel-lite instability (MSI) and Wnt mutations (19/29 vs. 7/17; 16/23 vs. 1/14, p=2.2×10(−4); 15/26 vs. 2/15, p=0.006; 14/26 vs. 4/20, p=0.02) but a lower frequency of B-raf proto-oncogene, serine/threonine kinase (BRAF) mutations (7/30 vs. 12/20, p=0.0089) than the distal form. CRC was more frequent in cases of Kirsten rat sarcoma viral oncogene homolog (KRAS)-associated proximal/whole-colon SPP-FHP/CRC than in the remaining cases (4/4 vs. 1/8, p=0.01). Thus, SPP-FHP/CRC appears to be a specific entity, presenting two forms, proximal/whole-colon and distal, which differ in the underlying tumor initiation pathways. Early MGMT and MMR gene deficiency in the former may underlie an inherited susceptibility to genotoxic stress. D.A. Spandidos 2016-09 2016-07-05 /pmc/articles/PMC4990292/ /pubmed/27430658 http://dx.doi.org/10.3892/ijmm.2016.2666 Text en Copyright: © Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Silva, Patrícia Albuquerque, Cristina Lage, Pedro Fontes, Vanessa Fonseca, Ricardo Vitoriano, Inês Filipe, Bruno Rodrigues, Paula Moita, Susana Ferreira, Sara Sousa, Rita Claro, Isabel Leitão, Carlos Nobre Chaves, Paula Pereira, António Dias Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities |
title | Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities |
title_full | Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities |
title_fullStr | Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities |
title_full_unstemmed | Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities |
title_short | Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities |
title_sort | serrated polyposis associated with a family history of colorectal cancer and/or polyps: the preferential location of polyps in the colon and rectum defines two molecular entities |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990292/ https://www.ncbi.nlm.nih.gov/pubmed/27430658 http://dx.doi.org/10.3892/ijmm.2016.2666 |
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