Better diagnosis of a cancer predisposition syndrome in children

CMMRD syndrome (Constitutional Mismatch Repair Deficiency) is a cancer predisposition syndrome that is rare but very aggressive and penetrating: 90% of affected children will develop a tumor before reaching the age of 20.

The cause is inherited mutations in the genes responsible for correcting DNA mismatches. The presence of multiple pseudogenes and the identification of variants of unknown significance make genetic diagnosis difficult. Clinically, it is also not easy to identify because its range of manifestations is wide and overlaps with other syndromes.

To address these problems, an international research group has developed and validated the hs-MSI genetic test. By analysing the errors that accumulate in 192 repetitive regions of the genome called microsatellites, this test determines from a blood sample whether the patient suffers from CMMRD or not.

The team was led by Drs. Gabriel Capellá and Marta Pineda and included researchers from the Bellvitge Biomedical Research Institute (IDIBELL), located in Hospitalet de Llobregat and one of the CERCA institutions of the Generalitat de Catalunya, the Catalan Institute of Oncology (ICO) in Hospitalet de Llobregat, and the Biomedical Research Network on Cancer Centre (CIBERONC), in Spain.

The authors of the study have also demonstrated how the test detects microsatellite errors with high sensitivity in all types of tumours caused by the syndrome, which represents a great improvement compared to traditional tests, which had a sensitivity of 18%. The identification of this characteristic makes them candidates for treatment with immunotherapy, which allows improving the clinical prognosis of children.

Members of the research team. (Photo: IDIBELL)

As explained by Dr. Fátima Marín, the first author of this study, “with this study we confirm the effectiveness of the hs-MSI test to diagnose CMMRD. The test is expected to be implemented in the Molecular Diagnostic Unit of the ICO and be accessible to healthcare professionals.” In addition, the doctor indicates that “a study has been started at a national level in which this test is carried out on all children with certain types of pediatric cancer to improve the identification of CMMRD and thus offer more effective treatments and better genetic counseling to affected families.”

The study is titled “A Validated Highly Sensitive Microsatellite Instability Assay Accurately Identifies Individuals Harboring Biallelic Germline PMS2 Pathogenic Variants in Constitutional Mismatch Repair Deficiency.” And it has been published in the academic journal Clinical Chemistry. (Source: IDIBELL)