Dados do Trabalho

Name: Next Frontiers to Cure Cancer
Start: 2023-09-15
End: 2023-09-16
Location: Expo Center Norte (Pavilhão Amarelo)

Título

MUTATIONAL SIGNATURE IN BREAST CANCER AND BRAIN METASTASIS

Introdução

Breast cancer is the leading cause of cancer-related deaths among women in Brazil. When diagnosed in advanced stages, survival rate is reduced and 90% of women in stage IV dies of metastatic complications. Brain is one of the most common metastatic sites in breast cancer patients, and even though it is a site with poor prognosis, the mutational profile of brain tumors is poorly described in the literature. Therefore, we understand that the identification of this profile may contribute to elucidate mechanisms associated with tumor progression.

Objetivo

The aim of this study was to identify a mutacional signature in breast tumors and brain metastases.

Métodos

This study was approved by Research Ethics Committee of the Barretos Cancer Hospital - Pio XII Foundation (1888/2019). DNA was extracted from paired samples of cryopreserved buffy-coat and paraffin material of breast tumors and brain metastases, from nine patients, to perform whole exome sequencing using Illumina platform. The exome sequenced was aligned to a reference genome, their duplicated regions were selected followed by the identification of somatic single nucleotide variants (SNVs), insertions and deletions (INDELs) and copy number variation (CNV). Filters to exclude germline mutations was added to normal tissue data and the mutational profile were identified following Koh et al. as reference.

Resultados

We identified somatic variants in driver genes related to breast cancer as described at CGI (Cancer Genome Interpreter) platform, such as ESR1, PIK3CA, TP53, FGFR3, and ERCC2. Also, breast tumors and brain metastases showed different profiles of amplifications and deletions. A mutational signature associated with trinucleotide was identified and related to defects in mismatch repair mechanisms.

Conclusões

These data suggest a different mutational profile in the primary tumor and brain metastasis, bringing new perspectives in identifying mechanisms associated with breast tumor progression.