María Arriba1, Ricardo Sánchez1, Daniel Rueda2, Laura Gómez3, Juan L García4, Yolanda Rodríguez5, José Antonio Pajares6, Jessica Pérez4, Miguel Urioste7, Rogelio González Sarmiento4, José Perea8. 1. Digestive Cancer Research Group, Centre for Biomedical Research, 12 de Octubre University Hospital, Madrid, Spain. 2. Molecular Biology Laboratory, 12 de Octubre University Hospital, Madrid, Spain. 3. UGC de Laboratorios, Hospital Universitario San Agustín, Linares, Jaen, Spain. 4. Biomedical Research Institute of Salamanca (Instituto de Investigación Biomédica de Salamanca), University Hospital of Salamanca-Universidad de Salamanca/Centro Superior de Investigaciones Científicas, Salamanca, Spain; Institute of Molecular and Cellular Biology of Cancer (Instituto de Biología Molecular y Celular del Cáncer), University of Salamanca-Centro Superior de Investigaciones Científicas, Salamanca, Spain. 5. Department of Pathology, 12 de Octubre University Hospital, Madrid, Spain. 6. Department of Digestive Diseases, Gregorio Marañón General University Hospital, Madrid, Spain. 7. Familial Cancer Clinical Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (Centro Nacional de Investigaciones Oncológicas), Madrid, Spain; Center for Biomedical Network Research on Rare Diseases (Centro de Investigación Biomédica en Red de Enfermedades Raras), Institute of Health Carlos III, Madrid, Spain. 8. Digestive Cancer Research Group, Centre for Biomedical Research, 12 de Octubre University Hospital, Madrid, Spain; Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain. Electronic address: josepereag@hotmail.com.
Abstract
BACKGROUND: Two or more primary colorectal tumors coexisting at the time of diagnosis are considered to be synchronous tumors. It is estimated that synchronous colorectal cancer (SCRC) only accounts for 1.1% to 8.1% of all colorectal cancers (CRCs), and its molecular basis is still poorly understood. PATIENTS AND METHODS: We evaluated the microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) statuses in a series of 49 patients (98 tumors) diagnosed with sporadic SCRC at the 12 de Octubre University Hospital with the aim of improving the molecular characterization of this type of tumor. We considered Lynch syndrome, familial adenomatous polyposis, and MUTYH-associated polyposis (MAP) as exclusion criteria. RESULTS: Molecular subgrouping on the basis of MSI and CIMP enabled us to define 4 groups that corresponded to the molecular classification proposed for single-tumor CRC. We observed a significant predominance of MSI tumors at the right side regardless of the methylation pattern, and a significant prevalence of microsatellite-stable tumors either at the left side or throughout the entire colon (P = .026). Furthermore, we defined some molecular features frequently observed in sporadic SCRC such as a low-frequency of MSI (8.2%). We observed a high concordance in terms of MSI between simultaneous tumors (93.9%) and a lower concordance in terms of CIMP (51%) between such tumors. CONCLUSION: Our findings support the hypothesis that SCRC involves an environmental rather than a genetic component in which various etiologic factors might modify tumor progression. Further studies are required to refine the molecular characterization of SCRC.
BACKGROUND: Two or more primary colorectal tumors coexisting at the time of diagnosis are considered to be synchronous tumors. It is estimated that synchronous colorectal cancer (SCRC) only accounts for 1.1% to 8.1% of all colorectal cancers (CRCs), and its molecular basis is still poorly understood. PATIENTS AND METHODS: We evaluated the microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) statuses in a series of 49 patients (98 tumors) diagnosed with sporadic SCRC at the 12 de Octubre University Hospital with the aim of improving the molecular characterization of this type of tumor. We considered Lynch syndrome, familial adenomatous polyposis, and MUTYH-associated polyposis (MAP) as exclusion criteria. RESULTS: Molecular subgrouping on the basis of MSI and CIMP enabled us to define 4 groups that corresponded to the molecular classification proposed for single-tumor CRC. We observed a significant predominance of MSI tumors at the right side regardless of the methylation pattern, and a significant prevalence of microsatellite-stable tumors either at the left side or throughout the entire colon (P = .026). Furthermore, we defined some molecular features frequently observed in sporadic SCRC such as a low-frequency of MSI (8.2%). We observed a high concordance in terms of MSI between simultaneous tumors (93.9%) and a lower concordance in terms of CIMP (51%) between such tumors. CONCLUSION: Our findings support the hypothesis that SCRC involves an environmental rather than a genetic component in which various etiologic factors might modify tumor progression. Further studies are required to refine the molecular characterization of SCRC.
Authors: José Perea; Juan L García; Luis Corchete; Eva Lumbreras; María Arriba; Daniel Rueda; Sandra Tapial; Jessica Pérez; Victoria Vieiro; Yolanda Rodríguez; Lorena Brandáriz; Mariano García-Arranz; Damián García-Olmo; Ajay Goel; Miguel Urioste; Rogelio González Sarmiento Journal: Int J Cancer Date: 2018-10-16 Impact factor: 7.396
Authors: María Arriba; Carmen Sánchez; Alfredo Vivas; O A Nutu; Daniel Rueda; Sandra Tapial; Yolanda Rodríguez; Lorena Brandáriz; Juan L García; Damián García-Olmo; Ajay Goel; Rogelio González-Sarmiento; Miguel Urioste; José Perea Journal: PLoS One Date: 2019-05-16 Impact factor: 3.240
Authors: Sandra Tapial; Daniel Rueda; María Arriba; Juan Luis García; Lorena Brandáriz; Jessica Pérez; Yolanda Rodríguez; Damián García-Olmo; Rogelio González-Sarmiento; Miguel Urioste; José Perea Journal: Br J Cancer Date: 2018-01-02 Impact factor: 7.640