Evolutionary history of human colitis-associated colorectal cancer
| Autor: | Baker, Ann-Marie, Cross, William, Curtius, Kit, Al Bakir, Ibrahim, Choi, Chang-Ho Ryan, Davis, Hayley Louise, Temko, Daniel, Biswas, Sujata, Martinez, Pierre, Williams, Marc J, Lindsay, James O, Feakins, Roger, Vega, Roser, Hayes, Stephen J, Tomlinson, Ian P M, McDonald, Stuart A C, Moorghen, Morgan, Silver, Andrew, East, James E, Wright, Nicholas A, Wang, Lai Mun, Rodriguez-Justo, Manuel, Jansen, Marnix, Hart, Ailsa L, Leedham, Simon J, Graham, Trevor A |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Colonoscopy/methods colorectal cancer Polymorphism Single Nucleotide Risk Assessment Severity of Illness Index dysplasia Humans Colitis Ulcerative/genetics Phylogeny Manchester Cancer Research Centre ResearchInstitutes_Networks_Beacons/mcrc Inflammatory Bowel Disease Cell Transformation Neoplastic/genetics Colonoscopy Middle Aged Polymorphism Single Nucleotide/genetics Colorectal Neoplasms/genetics digestive system diseases Gene Expression Regulation Neoplastic Cell Transformation Neoplastic IBD - genetics Disease Progression Colitis Ulcerative Female Colorectal Neoplasms |
| Zdroj: | Baker, A-M, Cross, W, Curtius, K, Al Bakir, I, Choi, C-H R, Davis, H L, Temko, D, Biswas, S, Martinez, P, Williams, M J, Lindsay, J O, Feakins, R, Vega, R, Hayes, S J, Tomlinson, I P M, McDonald, S A C, Moorghen, M, Silver, A, East, J E, Wright, N A, Wang, L M, Rodriguez-Justo, M, Jansen, M, Hart, A L, Leedham, S J & Graham, T A 2018, ' Evolutionary history of human colitis-associated colorectal cancer ', Gut, vol. 68, no. 6, pp. 985-995 . https://doi.org/10.1136/gutjnl-2018-316191 Gut Baker, A, Cross, W, Curtius, K, Al Bakir, I, Choi, C R, Davis, H L, Temko, D, Biswas, S, Martinez, P, Williams, M J, Lindsay, J O, Feakins, R, Vega, R, Hayes, S J, Tomlinson, I P M, Mcdonald, S A C, Moorghen, M, Silver, A, East, J E, Wright, N A, Wang, L M, Rodriguez-justo, M, Jansen, M, Hart, A L, Leedham, S J & Graham, T A 2018, ' Evolutionary history of human colitis-associated colorectal cancer ', Gut, pp. gutjnl-2018-316191 . https://doi.org/10.1136/gutjnl-2018-316191 |
| Popis: | OBJECTIVE: IBD confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the evolutionary history of CA-CRC using multiregion sequencing.DESIGN: Exome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 patients with CA-CRC (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using single nucleotide polymorphism arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD; n=30), high-grade dysplasia (HGD; n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC.RESULTS: 10/12 tumours were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNA) per Mb, ~20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated ageing-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighbouring CA-CRC, indicating a precancer mutational field. CA-CRCs were often near triploid (40%) or near tetraploid (20%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated 'catastrophic' CNA increase.CONCLUSIONS: Evolutionary genomic analysis revealed precancer clones bearing extensive SNAs and CNAs, with progression to cancer involving a dramatic accrual of CNAs at HGD. Detection of the cancerised field is an encouraging prospect for surveillance, but punctuated evolution may limit the window for early detection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|