CCR EN EL ADULTO JOVEN, UNA ENTIDAD DIFERENTE
Speaker: Jessica Pérez García
Centro de Investigación del Cáncer (CIC-IBMCC), Salamanca
Salón de actos del Centro de Investigación del Cáncer
Early onset CRC (age< 50 years) (EOCRC), reaches up to 10% of the total CRC and has been increasing in recent years. Based on current trends, in 2030 the incidence rate for colon and rectal cancer will increase by 90.0% and 124.2% for patients 20 to 34 years of age and by 27.7% and 46.0% for patients 35 to 49 years of age. EOCRC presents distinctive characteristics with respect to those cases that arise in the older population (Late onset colorectal cancer: LOCRC). The criterion "early age" of onset is characteristic of hereditary cancers, being the most frequent hereditary CRC the Lynch syndrome (LS). Until a few years ago, most studies in relation to the EOCRC focused on this hereditary component, especially LS, demonstrating the importance of the age criterion when identifying cases of this syndrome. However, in recent studies, the proportion of EOCRC with a germline mutation in genes related to hereditary cancer does not reach 20% and do not explain the rising incidence. Therefore, the EOCRC is a heterogeneous group, which includes hereditary cases, others with family aggregation and sporadic forms. Recent studies have shown clinical, genetic and biological differences according to the age of onset of CRC, suggesting that age should be an important criterion for the subclassification of CRC.
A recent study conducted by our group analyzed extensively DNA copy number alterations (CNAs) between EOCRC and LOCRC. We found that 97.3% of all CRC tumors showed a high genomic instability index. The analysis revealed a recurrent deletion in the short arm of chromosome 16, specifically in the region 16p13.12-p13.11. This region encompasses a set of genes where, among others, ABCC6, PDXDC1, NTAN1, BFAR, NPIPA2, PLA2G10, RRN3, PKD1P6 and NOMO1 are included. We studied the clinical characteristics of EOCRC as well as the involvement of NOMO1 gene in CRC. qPCR analysis of NOMO1 in breast, ovarian, endometrium, head and neck cancer, as well as in glioblastoma, show that the gene is germline in all these tumors whereas EOCRC show deletion in 71% of cases. NGS analysis of tumors obtained from EOCRC patients with either germ-line or heterozygous deletion of NOMO1 with a panel that contains genes coding for proteins of the Nodal pathway show pathogenic missense mutations in different genes. Interestingly, NOMO1 gene was mutated in 50% of cases carrying NOMO1 heterozygous deletion.