BACKGROUND: We studied the overlap between the major (epi)genomic events microsatellite instability (MSI), the CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) in colorectal cancer (CRC), and whether specific (epi)genotypes were associated with CRC-related deaths. PATIENTS AND METHODS: Molecular analyses using tumor DNA were successful in 509 CRC cases identified within the Netherlands Cohort Study in the period 1989-1993. Follow-up for the vital status until May 2005 was 100%. RESULTS: MSI (12.6%), CIMP-only (5.3%), CIMP + CIN (13.4%), CIN-only (58.2%) and triple-negative tumors (10.6%) differed significantly regarding tumor localization, differentiation grade, initial adjuvant therapy (AT) use and genetic characteristics (P ≤ 0.03). CIMP-only, CIMP + CIN and triple-negative tumors, compared with CIN-only tumors, were significantly associated with a 3.67, 2.44 and 3.78-fold risk of CRC-related deaths after 2-year follow-up (95% confidence intervals, CIs, 1.70-7.91, 1.35-4.41 and 1.97-7.25, respectively), but not after late follow-up. MSI tumors were borderline significantly associated with a 0.40-fold risk of CRC-related deaths after late follow-up (95% CI 0.15-1.03). CONCLUSION(S): This is the first study to show that specific (epi)genotypes may hold a differential prognostic value that may vary over time. Although no specific treatment data were available, an explanation for the differential findings over time might be that (epi)genotypes modify therapy response.
BACKGROUND: We studied the overlap between the major (epi)genomic events microsatellite instability (MSI), the CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) in colorectal cancer (CRC), and whether specific (epi)genotypes were associated with CRC-related deaths. PATIENTS AND METHODS: Molecular analyses using tumor DNA were successful in 509 CRC cases identified within the Netherlands Cohort Study in the period 1989-1993. Follow-up for the vital status until May 2005 was 100%. RESULTS: MSI (12.6%), CIMP-only (5.3%), CIMP + CIN (13.4%), CIN-only (58.2%) and triple-negative tumors (10.6%) differed significantly regarding tumor localization, differentiation grade, initial adjuvant therapy (AT) use and genetic characteristics (P ≤ 0.03). CIMP-only, CIMP + CIN and triple-negative tumors, compared with CIN-only tumors, were significantly associated with a 3.67, 2.44 and 3.78-fold risk of CRC-related deaths after 2-year follow-up (95% confidence intervals, CIs, 1.70-7.91, 1.35-4.41 and 1.97-7.25, respectively), but not after late follow-up. MSI tumors were borderline significantly associated with a 0.40-fold risk of CRC-related deaths after late follow-up (95% CI 0.15-1.03). CONCLUSION(S): This is the first study to show that specific (epi)genotypes may hold a differential prognostic value that may vary over time. Although no specific treatment data were available, an explanation for the differential findings over time might be that (epi)genotypes modify therapy response.
Authors: Muriel X G Draht; Kim M Smits; Benjamin Tournier; Valerie Jooste; Caroline Chapusot; Beatriz Carvalho; Arjen H G Cleven; Sarah Derks; Kim A D Wouters; Eric J T Belt; Hein B A C Stockmann; Herman Bril; Matty P Weijenberg; Piet A van den Brandt; Adriaan P de Bruïne; James G Herman; Gerrit A Meijer; Françoise Piard; Veerle Melotte; Manon van Engeland Journal: Mol Oncol Date: 2014-02-02 Impact factor: 6.603
Authors: Niels F Jensen; Jan Stenvang; Mette K Beck; Barbora Hanáková; Kirstine C Belling; Khoa N Do; Birgitte Viuff; Sune B Nygård; Ramneek Gupta; Mads H Rasmussen; Line S Tarpgaard; Tine P Hansen; Eva Budinská; Per Pfeiffer; Fred Bosman; Sabine Tejpar; Arnaud Roth; Mauro Delorenzi; Claus L Andersen; Maria U Rømer; Nils Brünner; José M A Moreira Journal: Mol Oncol Date: 2015-02-24 Impact factor: 6.603
Authors: Y Y Juo; F M Johnston; D Y Zhang; H H Juo; H Wang; E P Pappou; T Yu; H Easwaran; S Baylin; M van Engeland; N Ahuja Journal: Ann Oncol Date: 2014-04-08 Impact factor: 32.976
Authors: M J Overman; L Adam; K Raghav; J Wang; B Kee; D Fogelman; C Eng; E Vilar; R Shroff; A Dasari; R Wolff; J Morris; E Karunasena; T R Pisanic; N Azad; S Kopetz Journal: Ann Oncol Date: 2018-01-01 Impact factor: 32.976