Highlights from

European Crohn’s and Colitis Organisation

Congress 2018

Vienna 14-17 February 2018

Shallow whole-genome sequencing predicts future cancer risk of LGD in UC

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 ‘progressor’ patients, with 27 LGD lesions, and 22 ‘non-progressor’ 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.

  1. Al Bakir K, et al. OP010. ECCO 2018.

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