NOMO-1 gene is deleted in early-onset colorectal cancer

Abstract

To characterize clinical features of a recurrent alteration in 16p13.12-p13.11 in Colorectal Cancer (CRC), mainly in Early-onset subgroup (EOCRC), and to assess the status of NOMO1, a gene located in that region, we analyzed differential clinicopathological, familial and molecular features of CRC subsets with and without alterations in the 16p13.12-p13.11, in global and EOCRC groups. We confirmed the region by fluorescence in-situ hybridization, and Quantitative Real-Time PCR analyzed the status of NOMO1 in different age-of-onset and Microsatellite Instability (MSI)-status CRC subsets. Both age-of-onset subsets were subsequently extended to further confirm NOMO1 gene changes. 16p13.12-p13.11 alterations were observed in 23.3% of CRCs, and was detected more frequently in EOCRC (33.3%) than in late-onset CRC (16.3%). The group with deletion in 16p showed a higher frequency of females and left-colon locations; a better prognosis; and higher Chromosomal Instability. Within the primary EOCRC population, 34 out of 34 of tumours showed a homozygous deletion in NOMO1, while in the late-onset population only 2 of the 17 tumours (11.7%) showed it. In the extended group, we found 61 out of 75 EOCRC patients (81.3%) with homozygous deletion and 7 patients (9.3%) with heterozygous deletion of NOMO1; moreover, in the new 50 late-onset patients, the proportions of deletions decreased. Microsatellite-Stable (MSS) EOCRC showed a very high proportion of homozygous loss of NOMO1 (54 of 59 cases, 91.5%), while the deletion was observed in only 7 out of 16 MSI cases. Deletion of NOMO1 is a molecular marker predominantly associated with EOCRC, particularly MSS subtypes.