Hereditary cancer predisposition syndromes are caused by pathogenic genetic variants that can be inherited by offspring and might increase the likelihood of having a tumor. Pathogenic variants that affect the PMS2 gene can cause Lynch syndrome, which predisposes to colon and endometrial cancer in adulthood, or CMMRD, a more serious condition associated with brain, haematological and colorectal tumours in childhood. In order to take preventive measures and choose the appropriate treatments in these patients, it is essential to diagnose the syndromes as soon as possible through genetic counseling and molecular diagnosis. This is a complicated process because, when analyzing the PMS2 gene by the currently used massive sequencing tests, it is very difficult to discriminate whether the genetic variants come from the PMS2 gene or from the PMS2CL pseudogene, as they share more than 99% identity. For this reason, until now, a more difficult and expensive technique, long PCR, was necessary to analyze the PMS2 gene.
To solve this problem, researchers from IDIBELL and ICO led by Drs. Conxi Lázaro and Marta Pineda have developed a bioinformatics algorithm to find all pathogenic variants, both from the gene and the pseudogene, through massive sequencing, making long PCR only necessary as a validation method. As Elisabet Munté, the first author of this article, explains, “it has been estimated that this algorithm will reduce the number of long PCR tests by up to 95%, which will speed up the PMS2 molecular diagnosis and provide a faster response to patients with suspected hereditary cancer“.
The article has been published in the Journal of Molecular Diagnostics and demonstrates the test validity with high sensitivity. This algorithm is openly accessible and can be implemented in molecular diagnostic laboratories that wish to do so.
This research counted on the Fundación Centro Médico de Asturias-IMOMA collaboration and analyzed samples from other Catalan hospitals (Vall d’Hebron Hospital, Sant Pau, Arnau de Vilanova and Parc Taulí). The study was possible thanks to the funds received by the La Marató de 3Cat Foundation 2019 call on rare diseases.
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).