A Novel BRCA1 Gene Mutation Detected With Breast Cancer in a Vietnamese Family by Targeted Next-Generation Sequencing: A Case Report

Abstract

Hereditary breast cancer is an inherited genetic condition, mainly caused by BRCA1 and BRCA2 gene mutations. These genetic changes can increase the risks of breast and ovarian cancers in women, while prostate and breast cancers in men. Especially, mutations in either BRCA1 or BRCA2 genes take important roles in early-onset breast cancer. The present study focused on a 47-year-old Vietnamese woman with breast cancer by applying targeted next-generation sequencing technique. A novel BRCA1 gene mutation, namely NM_007294.3 (BRCA1): c.4998insA (p. Tyr1666Terfs), was identified both in this patient and in some of the members in her family proved the fact that the mutated genes passed down through generations. This change may exponentially initiate breast cancer risks and become a valuable marker for exact clinical prognosis and treatment.

Keywords: BRCA1 gene mutation; breast cancer; early—onset period; family pedigree.

Figure 1.

The pedigree of a Vietnamese patient’s family in 3 generations with hereditary breast cancer. Squares and circles denote males and females, respectively. The red arrow indicates the main proband. Members have breast cancer clinically and carry gene mutation being denoted by black circles. People have a central dot seen as gene mutation carriers without disease. Brown symbols illustrate individuals who do not carry any mutant. Circles or squares crossed by a line represent member deceased.

Figure 2.

Immunostaining images (magnification 40×, scale bar 50µm). Hematoxylin and Eosin staining for tumor tissues (A). Immunohistochemistry staining for estrogen receptor (B); negative, progesterone receptor (C); negative, Her-2 (D); positive (+++) and Ki67 index 75% (E).

Figure 3.

A germline novel heterozygous insertion mutation location was identified by Sanger sequencing denoted by a red arrow (namely NM_007294.3 (BRCA1): c.4998insA (p.Tyr1666Terfs)).