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Focus on 16p13.3 Locus in Colon Cancer

BACKGROUND: With one million new cases of colorectal cancer (CRC) diagnosed annually in the world, CRC is the third most commonly diagnosed cancer in the Western world. Patients with stage I-III CRC can be cured with surgery but are at risk for recurrence. Colorectal cancer is characterized by the p...

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Autores principales: Mampaey, Evi, Fieuw, Annelies, Van Laethem, Thalia, Ferdinande, Liesbeth, Claes, Kathleen, Ceelen, Wim, Van Nieuwenhove, Yves, Pattyn, Piet, De Man, Marc, De Ruyck, Kim, Van Roy, Nadine, Geboes, Karen, Laurent, Stéphanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519182/
https://www.ncbi.nlm.nih.gov/pubmed/26222184
http://dx.doi.org/10.1371/journal.pone.0131421
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author Mampaey, Evi
Fieuw, Annelies
Van Laethem, Thalia
Ferdinande, Liesbeth
Claes, Kathleen
Ceelen, Wim
Van Nieuwenhove, Yves
Pattyn, Piet
De Man, Marc
De Ruyck, Kim
Van Roy, Nadine
Geboes, Karen
Laurent, Stéphanie
author_facet Mampaey, Evi
Fieuw, Annelies
Van Laethem, Thalia
Ferdinande, Liesbeth
Claes, Kathleen
Ceelen, Wim
Van Nieuwenhove, Yves
Pattyn, Piet
De Man, Marc
De Ruyck, Kim
Van Roy, Nadine
Geboes, Karen
Laurent, Stéphanie
author_sort Mampaey, Evi
collection PubMed
description BACKGROUND: With one million new cases of colorectal cancer (CRC) diagnosed annually in the world, CRC is the third most commonly diagnosed cancer in the Western world. Patients with stage I-III CRC can be cured with surgery but are at risk for recurrence. Colorectal cancer is characterized by the presence of chromosomal deletions and gains. Large genomic profiling studies have however not been conducted in this disease. The number of a specific genetic aberration in a tumour sample could correlate with recurrence-free survival or overall survival, possibly leading to its use as biomarker for therapeutic decisions. At this point there are not sufficient markers for prediction of disease recurrence in colorectal cancer, which can be used in the clinic to discriminate between stage II patients who will benefit from adjuvant chemotherapy. For instance, the benefit of adjuvant chemotherapy has been most clearly demonstrated in stage III disease with an approximately 30 percent relative reduction in the risk of disease recurrence. The benefits of adjuvant chemotherapy in stage II disease are less certain, the risk for relapse is much smaller in the overall group and the specific patients at risk are hard to identify. MATERIALS AND METHODS: In this study, array-comparative genomic hybridization analysis (array-CGH) was applied to study high-resolution DNA copy number alterations in 93 colon carcinoma samples. These genomic data were combined with parameters like KRAS mutation status, microsatellite status and clinicopathological characteristics. RESULTS: Both large and small chromosomal losses and gains were identified in our sample cohort. Recurrent gains were found for chromosome 1q, 7, 8q, 13 and 20 and losses were mostly found for 1p, 4, 8p, 14, 15, 17p, 18, 21 and 22. Data analysis demonstrated that loss of chromosome 4 is linked to a worse prognosis in our patients series. Besides these alterations, two interesting small regions of overlap were identified, which could be associated with disease recurrence. Gain of the 16p13.3 locus (including the RNA binding protein, fox-1 homolog gene, RBFOX1) was linked with a worse recurrence-free survival in our patient cohort. On the other hand, loss of RBFOX1 was only found in patients without disease recurrence. Most interestingly, above mentioned characteristics were also found in stage II patients, for whom there is a high medical need for the identification of new prognostic biomarkers. CONCLUSIONS: In conclusion, copy number variation of the 16p13.3 locus seems to be an important parameter for prediction of disease recurrence in colon cancer.
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spelling pubmed-45191822015-07-31 Focus on 16p13.3 Locus in Colon Cancer Mampaey, Evi Fieuw, Annelies Van Laethem, Thalia Ferdinande, Liesbeth Claes, Kathleen Ceelen, Wim Van Nieuwenhove, Yves Pattyn, Piet De Man, Marc De Ruyck, Kim Van Roy, Nadine Geboes, Karen Laurent, Stéphanie PLoS One Research Article BACKGROUND: With one million new cases of colorectal cancer (CRC) diagnosed annually in the world, CRC is the third most commonly diagnosed cancer in the Western world. Patients with stage I-III CRC can be cured with surgery but are at risk for recurrence. Colorectal cancer is characterized by the presence of chromosomal deletions and gains. Large genomic profiling studies have however not been conducted in this disease. The number of a specific genetic aberration in a tumour sample could correlate with recurrence-free survival or overall survival, possibly leading to its use as biomarker for therapeutic decisions. At this point there are not sufficient markers for prediction of disease recurrence in colorectal cancer, which can be used in the clinic to discriminate between stage II patients who will benefit from adjuvant chemotherapy. For instance, the benefit of adjuvant chemotherapy has been most clearly demonstrated in stage III disease with an approximately 30 percent relative reduction in the risk of disease recurrence. The benefits of adjuvant chemotherapy in stage II disease are less certain, the risk for relapse is much smaller in the overall group and the specific patients at risk are hard to identify. MATERIALS AND METHODS: In this study, array-comparative genomic hybridization analysis (array-CGH) was applied to study high-resolution DNA copy number alterations in 93 colon carcinoma samples. These genomic data were combined with parameters like KRAS mutation status, microsatellite status and clinicopathological characteristics. RESULTS: Both large and small chromosomal losses and gains were identified in our sample cohort. Recurrent gains were found for chromosome 1q, 7, 8q, 13 and 20 and losses were mostly found for 1p, 4, 8p, 14, 15, 17p, 18, 21 and 22. Data analysis demonstrated that loss of chromosome 4 is linked to a worse prognosis in our patients series. Besides these alterations, two interesting small regions of overlap were identified, which could be associated with disease recurrence. Gain of the 16p13.3 locus (including the RNA binding protein, fox-1 homolog gene, RBFOX1) was linked with a worse recurrence-free survival in our patient cohort. On the other hand, loss of RBFOX1 was only found in patients without disease recurrence. Most interestingly, above mentioned characteristics were also found in stage II patients, for whom there is a high medical need for the identification of new prognostic biomarkers. CONCLUSIONS: In conclusion, copy number variation of the 16p13.3 locus seems to be an important parameter for prediction of disease recurrence in colon cancer. Public Library of Science 2015-07-29 /pmc/articles/PMC4519182/ /pubmed/26222184 http://dx.doi.org/10.1371/journal.pone.0131421 Text en © 2015 Mampaey et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mampaey, Evi
Fieuw, Annelies
Van Laethem, Thalia
Ferdinande, Liesbeth
Claes, Kathleen
Ceelen, Wim
Van Nieuwenhove, Yves
Pattyn, Piet
De Man, Marc
De Ruyck, Kim
Van Roy, Nadine
Geboes, Karen
Laurent, Stéphanie
Focus on 16p13.3 Locus in Colon Cancer
title Focus on 16p13.3 Locus in Colon Cancer
title_full Focus on 16p13.3 Locus in Colon Cancer
title_fullStr Focus on 16p13.3 Locus in Colon Cancer
title_full_unstemmed Focus on 16p13.3 Locus in Colon Cancer
title_short Focus on 16p13.3 Locus in Colon Cancer
title_sort focus on 16p13.3 locus in colon cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519182/
https://www.ncbi.nlm.nih.gov/pubmed/26222184
http://dx.doi.org/10.1371/journal.pone.0131421
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