N90: Argentinean Lynch syndrome registry: Experience from Rosario

E. Spirandelli¹, A. Naves², S. Chialina³, F. Spirandelli¹

1 – Servicio de Coloproctologia y Asesoria Genetica, Hospital Español Rosario, Rosario, Argentina. 2 – Instituto de Histopatologia, Rosario, Argentina. 3 – Laboratorio Stem Rosario, Rosario, Argentina.

Aim: There is still no national hereditary or familial cancer registers in Argentina. With the mission of improving detection, prevention and management of high risk cancer population in Rosario, with a population of 1.198.528 inhabitants, the Asociación Civil de Estudio, Tratamiento, Investigación de Enfermedades Heredo familiares de Rosario (ACETHIER) was established as a genetic reference center in 2005.

Methods: Hospital Español is used to identify suspected Lynch syndrome (LS) families. The Amsterdam criteria (AMS) or Bethesda guidelines were mostly used to select cases for screening by immunohistochemistry (IHC) and/or microsatellite instability (MSI) analysis. Genetic testing was generally based on Sanger sequencing of MLH1, MSH2, MSH6, PMS2 and/or EPCAM. By the advent of next generation sequencing (NGS), we are recently using 17- multigene panels including: APC, BMPR1A, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, MUTYH, POLD1, POLE, PTEN SMAD4, STK11, PT53, EPCAM and GREM1(Ambry Genetics, USA). Patients are informed about their inclusion into the registry, which generally contained data on family history, clinical information, age at onset and results of DNA testing or tumour screening in the diagnosis of LS. Written informed consent was obtained from all patients during genetic counselling sessions.

Results: From our registry, 61 suspected families fulfilled AMS criteria or Bethesda guidelines. Seventeen families (28%) had MMR deficiency and underwent genetic MMR testing. Path_ MLH1 variants was identified in 3 (21%) families, path_ MSH2/EPCAM variants in 11 (72%) families and path_ PMS2 variants in 1 family (7%). LS carriers have been identified with a mean age of 37.5 years (range 18-57) and a mean of 13 follow-up years.

Conclusion: The path_MSH2 variants are the most frequently identified in our registry and we provides support to set or improve LS genetic testing in South America. In addition, despite the small number of our registry, we described patients with a young age of onset and/or a positive family history of LS-associated cancers without an identified path_MMR variant, and may suggest the involvement of pathogenic variants in as yet undiscovered genes.

Acknowledgement: We would like to thank Mev Dominguez-Valentin (Oslo University Hospital, Oslo, Norway), for her unconditional support and her effort, to be able to join all the research groups in Hereditary Colorectal Cancer from South America. She can lead this great Group, and we know that we will continue to grow.