TY - JOUR
T1 - Molecular pathways in post-colonoscopy versus detected colorectal cancers
T2 - results from a nested case–control study
AU - Bogie, Roel M. M.
AU - le Clercq, Chantal M. C.
AU - Voorham, Quirinus J. M.
AU - Cordes, Martijn
AU - Sie, Daoud
AU - Rausch, Christian
AU - van den Broek, Evert
AU - de Vries, Sara D. J.
AU - van Grieken, Nicole C. T.
AU - Riedl, Robert G.
AU - Sastrowijoto, Prapto
AU - Speel, Ernst-Jan
AU - Vos, Rein
AU - Winkens, Bjorn
AU - van Engeland, Manon
AU - Ylstra, Bauke
AU - Meijer, Gerrit A.
AU - Masclee, Ad A. M.
AU - Carvalho, Beatriz
N1 - Funding Information: AM received funding from the Dutch Cancer Society, from the Dutch Organization for Health Research and Development, from Pentax Europe GmBH. AM has given scientific advice to Kyowa Kirin, Bayer, and Takeda. BC has several patents pending. The remaining authors declare no competing interests. Funding Information: RB and CLC received an unrestricted educational grant from Pentax Medical BV. BY contributed to the manuscript with the support of the Dutch Cancer Society (Grant No. KWF 2015-7882). Funding Information: We thank the technicians of the pathology laboratory at the Netherlands Cancer Institute in Amsterdam for their help with the DNA isolations. We thank the Tumour Genome Analysis Core at Amsterdam UMC for low-coverage WGS and cancer-related gene panel-targeted sequencing. We thank the Genomics Core Facility at the Netherlands Cancer Institute for cancer-related gene panel-targeted sequencing. We thank the technicians of the pathology laboratory at the Maastricht University Medical Centre for their help with the CIMP analysis. We thank Dr. Silvia Sanduleanu for her contribution to the origin of this study. We acknowledge that a part of this work has been presented at the UEGW 2016 in Vienna [57]. This work was performed within the frame of the COST Action [CA17118], supported by COST (European Cooperation in Science and Technology). Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021
Y1 - 2021
N2 - Background: Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case–control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). Methods: Whole-genome chromosomal copy number changes and mutation status of genes commonly affected in CRC were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status was also determined. Results: In total, 122 PCCRCs and 98 DCRCs with high-quality DNA were examined. PCCRCs were more often located proximally (P < 0.001), non-polypoid appearing (P = 0.004), early stage (P = 0.009) and poorly differentiated (P = 0.006). PCCRCs showed significantly less 18q loss (FDR < 0.2), compared to DCRCs. No significant differences in mutations were observed. PCCRCs were more commonly CIMP high (P = 0.014) and MSI (P = 0.029). After correction for tumour location, only less 18q loss remained significant (P = 0.005). Conclusion: Molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. These together with the clinical features observed support the hypothesis that SSLs and non-polypoid CRNs are contributors to the development of PCCRCs. The future focus should be directed at improving the detection and endoscopic removal of these non-polypoid CRN and SSLs. Clinical trial registration: NTR3093 in the Dutch trial register (www.trialregister.nl).
AB - Background: Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case–control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). Methods: Whole-genome chromosomal copy number changes and mutation status of genes commonly affected in CRC were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status was also determined. Results: In total, 122 PCCRCs and 98 DCRCs with high-quality DNA were examined. PCCRCs were more often located proximally (P < 0.001), non-polypoid appearing (P = 0.004), early stage (P = 0.009) and poorly differentiated (P = 0.006). PCCRCs showed significantly less 18q loss (FDR < 0.2), compared to DCRCs. No significant differences in mutations were observed. PCCRCs were more commonly CIMP high (P = 0.014) and MSI (P = 0.029). After correction for tumour location, only less 18q loss remained significant (P = 0.005). Conclusion: Molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. These together with the clinical features observed support the hypothesis that SSLs and non-polypoid CRNs are contributors to the development of PCCRCs. The future focus should be directed at improving the detection and endoscopic removal of these non-polypoid CRN and SSLs. Clinical trial registration: NTR3093 in the Dutch trial register (www.trialregister.nl).
UR - http://www.scopus.com/inward/record.url?scp=85121333360&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41416-021-01619-z
DO - https://doi.org/10.1038/s41416-021-01619-z
M3 - Article
C2 - 34912077
SN - 0007-0920
JO - British journal of cancer
JF - British journal of cancer
ER -