Work

Uncovering the genetic variation spectrum of colorectal polyposis from a multicentre cohort in China

Year: 2025

Type: article

Abstract: Background: There is a lack of multicentre studies on the genetic spectrum of colorectal polyposis in China.Methods: We utilized a 139-gene next-generation sequencing (NGS) panel and multiplex ligation-dependent probe amplification (MLPA) to detect germline variants in patients with colorectal polyposis. Sanger sequencing was used for pedigree verification.Results: Among the 120 patients with adenomatous polyposis, 88 carried pathogenic/likely pathogenic germline variants in key genes associated with hereditary colorectal cancer, including APC (85 patients), MUTYH (2 patients) and MSH2 (1 patient). In addition, NGS can serendipitously reveal other causative variants. One patient carried both the APC variant and the BRCA2 variant, which are inherited from the paternal and maternal lines, respectively. Compared with published data from Western populations, the APC mutation rate in this study was higher and included mainly nonsense mutations, whereas frameshift mutations were predominant in Western populations. We divided all 120 patients into three groups according to the number of polyps: 10–19 polyps (n=7), 20–99 polyps (n=37), and greater than or equal to 100 polyps (n=76) and found that none of these 7 patients with 10–19 polyps were diagnosed with hereditary tumours. To explore the pathogenesis of polyposis, in addition to the 3 patients with DUOX2-associated polyposis identified in our previous study, we also analysed the pathogenic or likely pathogenic variants carried by the other 29 patients. We found that the FANCL variant detected in one patient did not show obvious cosegregation among pedigree members. Although GJB2 V37I had a higher mutation rate in the mutation-negative population than in the normal population, there is currently insufficient evidence to support the direct association between this mutation and the occurrence of colorectal polyposis.Conclusion: This is the first multicentre clinical study on the genetic spectrum of colorectal polyposis in China. The APC mutation spectrum of colorectal polyposis in the Chinese population is quite different from that in the West. We suggest that for patients with fewer than 20 adenomas, genetic testing can be postponed.

Source: npj Precision Oncology

DOI: 10.1038/s41698-025-00864-2