Kaur Jaspreet, Chandrashekar Darshan S, Varga Zsuzsanna, Sobottka Bettina, Janssen Emiel, Gandhi Khanjan, Kowalski Jeanne, Kiraz Umay, Varambally Sooryanarayana, Aneja Ritu
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Department of Pathology-Molecular and Cellular, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Genes (Basel). 2023 Aug 25;14(9):1690. doi: 10.3390/genes14091690.
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 ( = 9); 8.2 variants/megabase in corresponding recurrent tumors ( = 9); and 7.3 variants/megabase in primary tumors that did not recur ( = 15). was the most frequently mutated gene in all groups. Mutations in and were more common in our dataset. No alterations in 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.
三阴性乳腺癌（TNBC）是一种分子复杂且异质性的乳腺癌亚型，具有独特的生物学特征和临床行为。尽管TNBC与转移和复发风险增加相关，但其转移的分子机制仍不清楚。我们对原发性TNBC和配对的复发性肿瘤进行了全外显子测序（WES）分析，以研究TNBC的基因谱。
从26例TNBC患者的35份福尔马林固定石蜡包埋组织样本中提取基因组DNA，进行WES分析。其中，15例为未复发的原发性肿瘤，11例为已复发的原发性肿瘤（9对原发性和复发性肿瘤）。对肿瘤进行单核苷酸变异和插入/缺失分析。
复发的原发性肿瘤的肿瘤突变负荷（TMB）为7.6个变异/兆碱基（n = 9）；相应复发性肿瘤的TMB为8.2个变异/兆碱基（n = 9）；未复发的原发性肿瘤的TMB为7.3个变异/兆碱基（n = 15）。TP53是所有组中最常发生突变的基因。在我们的数据集中，PIK3CA和AKT1的突变更为常见。在我们的数据集中未检测到BRCA1和BRCA2的改变。
我们发现原发性肿瘤和配对的复发性肿瘤之间具有相似的突变谱，这表明基因组特征在局部复发过程中可能得以保留。
