Genomic landscape of cancer driver genes in Omani breast cancers: a pilot study

The global rise in breast cancer (BC) incidence is mirrored in the Sultanate of Oman, where the median age of diagnosis is strikingly young at 47 years. This pilot study represents the first in the region to examine the genetic alterations of Omani BC biopsies and resected tumors and their correlations with patient characteristics using a targeted pan-cancer panel.

Utilizing the Oncomine Comprehensive Assay Plus, we profiled 40 BC biopsies alongside 22 matched post-neoadjuvant chemotherapy samples, identifying single-nucleotide variations (SNVs) and copy number variations (CNVs). Chi-Square and Fisher's Exact tests were used for categorical variables. In contrast, the Independent T-test and Levene test were used for continuous variables. Comparative analyses were conducted using the METABRIC and TCGA datasets to place these findings in a global context.

The data revealed molecular patterns between early-onset (under 50 years) and late-onset (50 years and older) cases. Notably, SNVs were predominant in late-onset tumors, while CNVs were more frequent in early-onset cases. PIK3CA SNVs emerged as a hallmark of late-onset BC, which persists across pre- and post-treatment stages. NTRK1 mutations were linked to late-onset cases at pre-treatment, while OR6F1 CNV was exclusive to early-onset tumors. The five genes with the highest CNV prevalence in the cohort were CDK12, ERBB2, BRIP1, and BLM, and they closely mirrored those found in global datasets. Correlations with clinical features identified CHEK2 alterations associated with high-grade tumors and luminal and HER2 type, while TP53 mutations were predominantly found in TNBC cases. Mutations in CBFB and GATA3 were predominantly enriched in luminal subtypes, and TSC1 mutations corresponded with smaller tumors, whereas FGFR4 SNVs were linked to nodal (N) status. Additionally, we identified 19 new SNV variants distributed across seven genes that were not recorded in the public databases.

This study sheds light on the genetic landscape of BC driver genes in Oman and the shared molecular traits with Western populations while uncovering unique regional alterations in NTRK1, OR6F1, and FGFR4. These findings highlight the need for region-specific insights to inform targeted therapies and personalized care, advancing the global understanding of BC biology.