Brewer Takae, Yehia Lamis, Bazeley Peter, Eng Charis
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, 44195, USA.
NPJ Genom Med. 2023 Jul 5;8(1):14. doi: 10.1038/s41525-023-00361-0.
Women with germline PTEN variants (PTEN hamartoma tumor syndrome, PHTS) have up to 85% lifetime risk of female breast cancer (BC). We previously showed that PHTS-derived BCs are distinct from sporadic BCs both at the clinical and genomic levels. In this study, we examined somatic copy number variations (CNV) and transcriptome data to further characterize the somatic landscape of PHTS-derived BCs. We analyzed exome sequencing data from 44 BCs from women with PHTS for CNV. The control group comprised of 558 women with sporadic BCs from The Cancer Genome Atlas (TCGA) dataset. Here, we found that PHTS-derived BCs have several distinct CNV peaks compared to TCGA. Furthermore, RNA sequencing data revealed that PHTS-derived BCs have a distinct immunologic cell type signature, which points toward cancer immune evasion. Transcriptomic data also revealed PHTS-derived BCs with pathogenic germline PTEN variants appear to have vitamin E degradation as a key pathway associated with tumorigenesis. In conclusion, our study revealed distinct CNV x transcript features in PHTS-derived BCs, which further facilitate understanding of BC biology arising in the setting of germline PTEN mutations.
携带种系PTEN变异（PTEN错构瘤肿瘤综合征，PHTS）的女性患女性乳腺癌（BC）的终生风险高达85%。我们之前表明，源自PHTS的乳腺癌在临床和基因组水平上均与散发性乳腺癌不同。在本研究中，我们检查了体细胞拷贝数变异（CNV）和转录组数据，以进一步描绘源自PHTS的乳腺癌的体细胞图谱特征。我们分析了44例来自患有PHTS的女性的乳腺癌的外显子组测序数据以检测CNV。对照组由来自癌症基因组图谱（TCGA）数据集的558例患有散发性乳腺癌的女性组成。在此，我们发现与TCGA相比，源自PHTS的乳腺癌有几个不同的CNV峰。此外，RNA测序数据显示，源自PHTS的乳腺癌具有独特的免疫细胞类型特征，这指向癌症免疫逃逸。转录组数据还显示，携带致病性种系PTEN变异的源自PHTS的乳腺癌似乎将维生素E降解作为与肿瘤发生相关的关键途径。总之，我们的研究揭示了源自PHTS的乳腺癌中不同的CNV×转录特征，这进一步有助于理解在种系PTEN突变背景下发生的乳腺癌生物学特性。
