The burden of chromosomal copy number alterations (CNAs) in precursor LGD relative to that in HGD/CRC has not yet been defined. Therefore, the correlation between LGD CNA burden and future CRC risk is unknown.
Researchers used shallow whole-genome sequencing to investigate these matters [3]. Shallow whole-genome sequencing is a novel, cost-effective technique for high-resolution CNA assessment in formalin-fixed, paraffin-embedded tissue.
A total of 19 UC proctocolectomy specimens with HGD/CRC were identified and 77 neoplastic regions (36 LGD, 34 HGD, and 7 CRC) were analysed. Subsequently, analysis was performed in 13 āprogressorā patients, with 27 LGD lesions, and 22 ānon-progressorā patients, with 26 LGD lesions. Progressors later developed HGD/CRC (after a median of 427 days) while non-progressors remained HGD/CRC-free for over five years.
The two patient groups were matched for age, gender, disease duration, and LGD location. The results showed that a median 12% of the genome of LGDs from proctocolectomy specimens showed CNAs, compared with 23% in HGD/CRC. Similarly, the number of CNA events was greater in HGD/CRC than in LGD (P<0.001). Multiple CNAs involving key driver genes were more frequent in HGD/CRC compared with LGD (adjusted P<0.05). Both the maximal total CNA burden and number of CNA events were greater in LGD of progressors than in LGD of non-progressors (P<0.01).
A Kaplan-Meier analysis was carried out. The 25% of patients in this cohort exhibiting LGD with greatest CNA burden were significantly more likely to develop CRC/HGD than the remaining 75% (HR 5.1, P=0.001). This led the research group to conclude that LGD lesions demonstrate a surprising diversity in CNA burden. Some LGD lesions bear CNA profiles indistinguishable from HGD/CRC. Shallow whole-genome sequencing has potential translational utility, by stratifying patients with LGD according to risk of progression to HGD/CRC.
- Al Bakir K, et al. OP010. ECCO 2018.
Posted on
Previous Article
« Overall manageable safety profile of tofacitinib in long-term use Next Article
Apremilast in active UC shows promising results »
« Overall manageable safety profile of tofacitinib in long-term use Next Article
Apremilast in active UC shows promising results »
Table of Contents: ECCO 2018
Featured articles
IBD diagnostics
IBD disease patterns and genetics
Novel treatment strategies
Efficacy and safety of biologics
Oncology in IBD
Surgery for IBD
Related Articles
May 28, 2018
Combining new drugs with different mechanisms
Ā© 2024 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy