Whole-Exome Sequencing Reveals High Mutational Concordance between Primary and Matched Recurrent Triple-Negative...

Triple-negative breast cancer (TNBC) is a molecularly complex and heterogeneous breast cancer subtype with distinct biological features and clinical behavior. Although TNBC is associated with an increased risk of metastasis and recurrence, the molecular mechanisms underlying TNBC metastasis remain unclear. We performed whole-exome sequencing (WES) analysis of primary TNBC and paired recurrent tumors to investigate the genetic profile of TNBC.

Genomic DNA extracted from 35 formalin-fixed paraffin-embedded tissue samples from 26 TNBC patients was subjected to WES. Of these, 15 were primary tumors that did not have recurrence, and 11 were primary tumors that had recurrence (nine paired primary and recurrent tumors). Tumors were analyzed for single-nucleotide variants and insertions/deletions.

The tumor mutational burden (TMB) was 7.6 variants/megabase in primary tumors that recurred (n = 9); 8.2 variants/megabase in corresponding recurrent tumors (n = 9); and 7.3 variants/megabase in primary tumors that did not recur (n = 15). MUC3A was the most frequently mutated gene in all groups. Mutations in MAP3K1 and MUC16 were more common in our dataset. No alterations in PI3KCA were detected in our dataset.

We found similar mutational profiles between primary and paired recurrent tumors, suggesting that genomic features may be retained during local recurrence.