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

Background/

Objectives

Multilocus Inherited Neoplasia Alleles Syndrome (MINAS) is defined by the presence of germline pathogenic or likely pathogenic variants in two or more distinct cancer susceptibility genes (CSGs) in the same individual. Although carriers may present more complex phenotypes, the clinical and molecular spectrum of MINAS remains poorly characterized, particularly in underrepresented populations. We aim to describe this phenomenon in a cohort of individuals from a Chilean institution.

Methods

We retrospectively reviewed individuals evaluated at the Oncogenetic Counseling Unit of Fundación Arturo López Pérez (FALP) between 2020 and 2026 who underwent hereditary cancer multi-gene panel testing. Cases fulfilling MINAS criteria were described. We analyzed the association between MINAS and age at cancer diagnosis or multiple primary cancers, and reviewed reported cases with the same gene combinations.

Results

From 1962 individuals tested, 398 harbored a pathogenic or likely pathogenic variant, and 14 fulfilled MINAS criteria, yielding a prevalence of 3.51% among positive cases. Breast cancer was the most common tumor type (76.9%), and ATM and CDKN2A were the most frequently involved genes. MINAS was significantly associated with a younger age at cancer diagnosis, but not with multiple primary cancers.

Conclusions

MINAS prevalence in our cohort and the association with a younger diagnosis of cancer was consistent with published series. We identified seven previously unreported gene combinations, and common founder variants shifted the pattern away from predominantly BRCA-associated combinations. Despite the small sample size, this study adds relevant data from an underrepresented Latin American population.