SO03: Evaluation of a 25-gene panel in patients with suspected Lynch syndrome: preliminary results from the FAMOSA study

Balaguer1, J. Balmaña2, A. Sánchez1, T.Ocaña1, I. Esteban2, G. Llort3, R. Jover4, J. Cubiella5, M. Herráiz6, V. Hernández7, S. Martínez8, M.J. Oruezábal Moreno9, C. Garau10, S. Kohrrami11, A. Herreros de Tejada12, R. Morales13, J.M. Cano14, R. Serrano15, C. Guillén16, A.B. Beatriz Sánchez-Heras17, E. Adrover18, E. Carrasco2, N. Gadea2, J. Brunet19.

1 – Gastroenterology Department, Hospital Clínic, Barcelona, Spain. 2 – Medical Oncology Department, Vall d’Hebron Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain. 3 – Hospital Sabadell-Parc Taulí, Sabadell, Spain. 4 – Hospital General Universitario de Alicante, Spain. 5 – Complejo Hospitalario Ourense, Spain. 6 – Hospital Clínico Universidad de Navarra, Spain. 7 – Complejo Hospitalario Universitario de Vigo, Spain. 8 – Hospital de Mataró, Spain. 9 – Hospital Rey Juan Carlos, Spain. 10 – Hospital Son Llatzer, Palma de Mallorca, Spain. 11 – Hospital Son Espases, Palma de Mallorca, Spain. 12 – Hospital Universitario Puerta de Hierro, Madrid, Spain. 13 – Hospital La Mancha Centro, Spain. 14 – Hospital General de Ciudad Real, Spain. 15 – Hospital Reina Sofia de Córdoba, Spain. 16 – Hospital Ramón y Cajal, Madrid, Spain. 17 – Hospital General de Elche, Spain. 18 – Hospital Universitario General de Albacete, Spain. 19 – Hospital Josep Trueta de Girona, ICO, Spain


The role of multigene panels for hereditary cancer risk assessment is yet to be established. We aimed at describing the prevalence of cancer predisposition gene mutations identified by a multigene panel in individuals with suspected Lynch syndrome(LS).


We performed germline analysis with a next-generation sequencing 25-gene-panel(Myriad myRisk™ Hereditary Cancer) using DNA from 95 patients with suspected LS(endometrial cancer <50 y-o and/or fulfillment of revised Bethesda criteria) from Nov-2014 through March-2015 within the FAMOSA study. We classified all identified germline variants for pathogenicity and calculated the prevalence of pathogenic mutations and variants of uncertain clinical significance (VUS). We analyzed data on patients’ personal and family history of cancer.


We included 95 patients [female:46(48.5%), mean age:48.6+12]: 8(8.5%) with endometrial cancer and 87(91.5%) with colorectal cancer. Multigene panel testing identified 20(21%) patients with LS syndrome mutations(8MLH1, 7MSH2, 4MSH6, 1PMS2) and 1(1%) with a mutation in BRCA2 in a 35 y-o woman without personal/familial history of breast/ovarian cancer. In patients diagnosed with mutations in the MMR genes and prior molecular screening(n=9), two displayed MMR proficiency and 5 patients had a negative prior genetic result by conventional techniques.


In individuals with suspected Lynch syndrome, multigene panel testing identified unexpected high-penetrance mutations in 1% of cases. Parallel sequencing also detected a meaningful number of cases with previous false negative results.