Yang Po-Sheng, Chao Ying-Ting, Lung Chun-Fan, Liu Chien-Liang, Chang Yuan-Ching, Li Ker-Chau, Hsu Yi-Chiung
Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
Department of General Surgery, MacKay Memorial Hospital, Taipei, Taiwan.
Front Oncol. 2022 Jul 22;12:819555. doi: 10.3389/fonc.2022.819555. eCollection 2022.
Breast cancer is the most common invasive cancer in women worldwide. Next-generation sequencing (NGS) provides a high-resolution profile of cancer genome. Our study ultimately gives the insight for genetic screening to identify the minority of patients with breast cancer with a poor prognosis, who might benefit from the most intensive possible treatment. The detection of mutations can polish the traditional method to detect high-risk patients who experience poor prognosis, recurrence and death early. In total, 147 breast cancer tumors were sequenced with targeted sequencing using a RainDance Cancer Hotspot Panel. The average age of all 147 breast cancer patients in the study was 51.7 years, with a range of 21-77 years. The average sequencing depth was 5,222x (range 2,900x-8,633x), and the coverage was approximately 100%. A total of 235 variants in 43 genes were detected in 147 patients by high-depth Illumina sequencing. A total of 219 single nucleotide variations were found in 42 genes from 147 patients, and 16 indel mutations were found in 13 genes from 84 patients. After filtering with the 1000 Genomes database and for synonymous SNPs, we focused on 54 somatic functional point mutations. The functional point mutations contained 54 missense mutations in 22 genes. Additionally, mutation of genes within the RET, PTEN, CDH1, MAP2K4, NF1, ERBB2, RUNX1, PIK3CA, FGFR3, KIT, KDR, APC, SMO, NOTCH1, and FBXW7 in breast cancer patients were with poor prognosis. Moreover, TP53 and APC mutations were enriched in triple-negative breast cancer. APC mutations were associated with a poor prognosis in human breast cancer (log-rank P<0.001). Our study identified tumor mutation hotspot profiles in Taiwanese breast cancer patients, revealing new targetable gene mutations in Asian breast cancer patients.
乳腺癌是全球女性中最常见的浸润性癌症。下一代测序（NGS）可提供癌症基因组的高分辨率图谱。我们的研究最终为基因筛查提供了见解，以识别少数预后不良的乳腺癌患者，这些患者可能从最强化的治疗中获益。突变检测可以完善传统方法，以检测那些早期预后不良、复发和死亡风险高的患者。总共使用RainDance癌症热点面板对147个乳腺癌肿瘤进行了靶向测序。该研究中所有147名乳腺癌患者的平均年龄为51.7岁，年龄范围为21至77岁。平均测序深度为5222倍（范围为2900倍至8633倍），覆盖率约为100%。通过深度Illumina测序在147名患者中检测到43个基因中的235个变异。在147名患者的42个基因中发现了总共219个单核苷酸变异，在84名患者的13个基因中发现了16个插入缺失突变。在用千人基因组数据库进行筛选并针对同义单核苷酸多态性后，我们聚焦于54个体细胞功能性点突变。这些功能性点突变包含22个基因中的54个错义突变。此外，乳腺癌患者中RET、PTEN、CDH1、MAP2K4、NF1、ERBB2、RUNX1、PIK3CA、FGFR3、KIT、KDR、APC、SMO、NOTCH1和FBXW7基因的突变与预后不良有关。此外，TP53和APC突变在三阴性乳腺癌中富集。APC突变与人乳腺癌的不良预后相关（对数秩检验P<0.001）。我们的研究确定了台湾乳腺癌患者的肿瘤突变热点图谱，揭示了亚洲乳腺癌患者新的可靶向基因突变。
