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Open AccessArticle

Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-Onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer

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Surgery Department, “Infanta Leonor” University Hospital, 28031 Madrid, Spain
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Oncology Department, Ciudad Real General Hospital, 13005 Ciudad Real, Spain
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Molecular Medicine Unit- Department of Medicine, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca-SACYL-CSIC, 37007 Salamanca, Spain
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Surgery Department, “Fundación Jiménez Díaz” University Hospital, 28040 Madrid, Spain
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Health Research Institute-Fundación Jiménez Díaz University Hospital, 28040 Madrid, Spain
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Biochemistry Department, Gregorio Marañon University Hospital, 28007 Madrid, Spain
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Molecular Biology Laboratory, University Hospital “12 de Octubre”, 28041 Madrid, Spain
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Digestive Cancer Group, “12 de Octubre” Research Institute, 28041 Madrid, Spain
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Pathology Department, University Hospital “12 de Octubre”, 28041 Madrid, Spain
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Gastroenterology Department, University Hospital “12 de Octubre”, 28041 Madrid, Spain
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Centre for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, 28029 Madrid, Spain
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Oncology Department, University Hospital “12 de Octubre”, 28041 Madrid, Spain
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Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute, Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, USA
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Familial Cancer Clinical Unit, Spanish National Cancer Centre (CNIO), 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(4), 968; https://doi.org/10.3390/ijms20040968
Received: 17 December 2018 / Revised: 15 February 2019 / Accepted: 19 February 2019 / Published: 22 February 2019
(This article belongs to the Special Issue Basic and Translational Research in Colorectal Cancer)
Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification. View Full-Text
Keywords: early-onset colorectal cancer; late-onset colorectal cancer; microsatellite instability; chromosomal instability; CpG island methylator phenotype; tumor location. early-onset colorectal cancer; late-onset colorectal cancer; microsatellite instability; chromosomal instability; CpG island methylator phenotype; tumor location.
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Álvaro, E.; Cano, J.M.; García, J.L.; Brandáriz, L.; Olmedillas-López, S.; Arriba, M.; Rueda, D.; Rodríguez, Y.; Cañete, Á.; Arribas, J.; Inglada-Pérez, L.; Pérez, J.; Gómez, C.; García-Arranz, M.; García-Olmo, D.; Goel, A.; Urioste, M.; González-Sarmiento, R.; Perea, J. Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-Onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer. Int. J. Mol. Sci. 2019, 20, 968.

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