Intratumor Heterogeneity of Synchronous In Situ and Invasive Breast Carcinoma Revealed Using Multi-region Exome Sequencing

Abstract

Background/aim: Intratumor heterogeneity (ITH), defined as a tumor composed of multiple subclones with different characteristics, is widely reported in invasive breast carcinoma (IBC) and ductal carcinoma in situ (DCIS). This study aimed to assess the extent of ITH in synchronous DCIS-IBC at the genetic level.

Materials and methods: A total of 17 lesions from 5 patients were subjected to whole-exome sequencing. Nonsynonymous mutations and copy number aberrations were visualized to assess ITH.

Results: The most commonly mutated cancer-related genes in IBC and DCIS were RUNX1 (35.3%), PIK3CA (29.4%), and GATA3 (29.4%). There were no universally mutated cancer-related genes in all IBCs. All lesions harbored private mutations restricted to each lesion. Several DCIS lesions displayed a greater amount of genetic aberrations than the accompanying IBC, implying that a subset of DCIS was as advanced or more advanced than the synchronous IBC.

Conclusion: We herein demonstrated genetic ITH in DCIS lesions coexisting with IBC.

Keywords: Genetic heterogeneity; breast cancer; ductal carcinoma in situ; massively parallel sequencing.