Report of Multilocus Inherited Neoplasia Alleles Syndrome in a Chilean Oncology Institute: New Combinations and Genetic Landscape.

Coexistence in one individual of germline pathogenic variants in at least two distinct susceptibility genes, ATM and CDKN2A being most frequently involved in this cohort.

MINAS denotes the presence in one individual of germline pathogenic or likely pathogenic variants in at least two distinct cancer susceptibility genes, an entity whose clinical and molecular spectrum remains poorly characterised, particularly in under-represented populations. The authors retrospectively reviewed individuals assessed at the oncogenetic counselling unit of Fundación Arturo López Pérez in Chile between 2020 and 2026 who underwent hereditary cancer multigene panel testing. Of 1,962 individuals tested, 398 carried a pathogenic or likely pathogenic variant and 14 met MINAS criteria, a prevalence of 3.51% among positive cases, with breast cancer the most common tumour (76.9%) and ATM and CDKN2A the most frequently involved genes. MINAS status was significantly associated with younger age at cancer diagnosis but not with multiple primary cancers. Seven previously unreported gene combinations were identified, and the frequency of local founder variants shifted the pattern of associations away from the usual BRCA1 and BRCA2-centred combinations.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

What this Latin American cohort specifically adds is a MINAS profile dominated not by BRCA1 and BRCA2 but by ATM and CDKN2A, a direct consequence of local founder variants, a reminder that a first identified variant should not close panel interpretation, still a common reflex. With 14 cases, the association with younger age at diagnosis remains an unadjusted within-cohort observation with no decisional value. The real unresolved difficulty is management of these double carriers, where stacking both surveillance protocols remains empirical and unsupported by outcome data.

Analysis by Dr Thibaut Benquey