# Custom target-sequencing in triple-negative and luminal breast cancer from young Brazilian patients

## TL;DR

This study identifies key genetic drivers in breast cancer from young Brazilian women, highlighting TP53 in triple-negative and PIK3CA/GATA3 in luminal tumors.

## Contribution

The study introduces CACNA1E, GRHL2, and SMURF2 as potential novel cancer drivers in young breast cancer patients.

## Key findings

- TP53 mutations were found in 75% of triple-negative breast cancer samples, often alongside NF1, NOTCH1, or PTPN13.
- PIK3CA and GATA3 were the main drivers in luminal breast cancer, with GRHL2 and SMURF2 as candidates.
- CACNA1E was identified as a candidate driver in both triple-negative and luminal breast cancer subtypes.

## Abstract

•In breast cancer from young women:TP53 was affected in 75 % of TN samples, in concomitance with at least one additional driver gene, mainly NF1, NOTCH1 or PTPN13.•In TN tumors carrying a wild type TP53, other drivers were TSG, like ATR and NF1.•PIK3CA and GATA3 were the main cancer driver genes in luminal samples, and candidate drivers were GRHL2 and SMURF2.•CACNA1E is a candidate cancer driver in both luminal and TN samples.

In breast cancer from young women:

TP53 was affected in 75 % of TN samples, in concomitance with at least one additional driver gene, mainly NF1, NOTCH1 or PTPN13.

In TN tumors carrying a wild type TP53, other drivers were TSG, like ATR and NF1.

PIK3CA and GATA3 were the main cancer driver genes in luminal samples, and candidate drivers were GRHL2 and SMURF2.

CACNA1E is a candidate cancer driver in both luminal and TN samples.

To identify somatic mutations in tumors from young women with triple-negative or luminal breast cancer, through targeted sequencing and to explore the cancer driver potential of these gene variants.

A customized gene panel was assembled based on data from previous sequencing studies of breast cancer from young women. Triple-negative and luminal tumors and paired blood samples from young breast cancer patients were sequenced, and identified gene variants were searched for their driver potential, in databases and literature. Additionally, the authors performed an exploratory analysis using large, curated databases to evaluate the frequency of somatic mutations in this gene panel in tumors stratified by age groups (every 10 years).

A total of 28 young women had their tumoral tissue and blood samples sequenced. Using a customized panel of 64 genes, the authors could detect cancer drivers in 11/12 (91.7 %) TNBC samples and 11/16 (68.7 %) luminal samples. Among TNBC patients, the most frequent cancer driver was TP53, followed by NF1, NOTCH1 and PTPN13. In luminal samples, PIK3CA and GATA3 were the main cancer drivers, and other drivers were GRHL2 and SMURF2. CACNA1E was involved in both TN and luminal BC. The exploratory analysis also indicated a role for SMURF2 in luminal BC development in young patients.

The data further indicates that some cancer drivers are more common in a specific breast cancer subtype from young patients, such as TP53 in TNBC and PIK3CA and GATA3 in luminal samples. These results also provide additional evidence that some genes not considered classical cancer-causing genes, such as CACNA1E, GRHL2 and SMURF2 might be cancer drivers in this age group.