PDF(Pubmed)
Abstract：
UNASSIGNED: Various genomic alterations and genomic signatures, including ERBB2 amplification, mutations in PIK3CA, AKT1, and ESR1, and tumor mutational burden (TMB), have become important biomarkers for treatment selection in breast cancer (BC). This study aimed to investigate the mutational features of Chinese early-stage BC patients.
UNASSIGNED: Tumors and matched blood samples collected from 589 Chinese patients with early-stage BC were sequenced using a commercial gene panel consisting of 520 cancer-related genes to analyze all types of genomic alterations and estimate the TMB status.
UNASSIGNED: A total of 18 genes were found to be more frequently mutated (P<0.05) or amplified (P<0.05) in stage T3-4 tumors as compared with T1-2 tumors. A total of 18 genes were found to be differentially mutated (P<0.05) or amplified (P<0.05) in patients with lymph node metastasis than those without lymph node metastasis. Younger patients (≤35 years) were more frequently identified with mutations or gene amplifications in eleven genes (P<0.05). TMB >10mutations/Mb were found in 5.7% of our cohort. Although the TMB was similar for various molecular subtypes between our cohort and the BC cohort of The Cancer Genome Atlas (TCGA) study, the TMB were statistically different for HR+/HER-, HR+/HER2+, and triple-negative subtypes between our cohort and African Americans in the TCGA study. As compared to the TCGA BC cohort, our cohort had a much earlier median age of diagnosis (48 vs. 58 years, P<0.001), and had significantly lower frequency of triple-negative subtype (11.5% vs. 18.4%, P<0.001) and invasive lobular BC (2.4% vs. 19.0%, P<0.001). Further subgroup analyses revealed that mutation rates in various genes including TP53, ERBB2, and PIK3CA were distinct for patients who were younger (≤35 years), had triple-negative or invasive lobular BC in our cohort than in the TCGA cohort.
UNASSIGNED: This study revealed distinct mutational features of various molecular subtypes of early-stage BC among Chinese patients. Moreover, we provide new insights into the differences in early-stage BC between the East and West.
UNASSIGNED: Tumors and matched blood samples collected from 589 Chinese patients with early-stage BC were sequenced using a commercial gene panel consisting of 520 cancer-related genes to analyze all types of genomic alterations and estimate the TMB status.
UNASSIGNED: A total of 18 genes were found to be more frequently mutated (P<0.05) or amplified (P<0.05) in stage T3-4 tumors as compared with T1-2 tumors. A total of 18 genes were found to be differentially mutated (P<0.05) or amplified (P<0.05) in patients with lymph node metastasis than those without lymph node metastasis. Younger patients (≤35 years) were more frequently identified with mutations or gene amplifications in eleven genes (P<0.05). TMB >10mutations/Mb were found in 5.7% of our cohort. Although the TMB was similar for various molecular subtypes between our cohort and the BC cohort of The Cancer Genome Atlas (TCGA) study, the TMB were statistically different for HR+/HER-, HR+/HER2+, and triple-negative subtypes between our cohort and African Americans in the TCGA study. As compared to the TCGA BC cohort, our cohort had a much earlier median age of diagnosis (48 vs. 58 years, P<0.001), and had significantly lower frequency of triple-negative subtype (11.5% vs. 18.4%, P<0.001) and invasive lobular BC (2.4% vs. 19.0%, P<0.001). Further subgroup analyses revealed that mutation rates in various genes including TP53, ERBB2, and PIK3CA were distinct for patients who were younger (≤35 years), had triple-negative or invasive lobular BC in our cohort than in the TCGA cohort.
UNASSIGNED: This study revealed distinct mutational features of various molecular subtypes of early-stage BC among Chinese patients. Moreover, we provide new insights into the differences in early-stage BC between the East and West.
摘要：
■各种基因组改变和基因组特征，包括ERBB2扩增，PIK3CA中的突变，AKT1和ESR1和肿瘤突变负荷（TMB），已成为乳腺癌（BC）治疗选择的重要生物标志物。本研究旨在探讨中国早期BC患者的突变特征。
使用由520个癌症相关基因组成的商业基因组对589例中国早期BC患者的肿瘤和匹配的血液样本进行测序，以分析所有类型的基因组改变并估计TMB状态。
■发现在T3-4期肿瘤中，与T1-2期肿瘤相比，共有18个基因更频繁地突变（P<0.05）或扩增（P<0.05）。发现有淋巴结转移的患者与无淋巴结转移的患者相比，共有18个基因发生了差异突变（P<0.05）或扩增（P<0.05）。年龄较小的患者（≤35岁）在11个基因中发现突变或基因扩增的频率更高（P<0.05）。在我们队列的5.7%中发现TMB>10突变/Mb。尽管在我们的队列和癌症基因组图谱（TCGA）研究的BC队列之间，各种分子亚型的TMB相似，HR+/HER-的TMB有统计学差异，HR+/HER2+,在TCGA研究中，我们的队列与非裔美国人之间存在三阴性亚型。与TCGABC队列相比，我们的队列诊断的中位年龄要早得多(48岁vs.58年,P<0.001)，并且三阴性亚型的频率明显较低(11.5%vs.18.4%,P<0.001）和侵袭性小叶BC（2.4%vs.19.0%,P<0.001)。进一步的亚组分析显示，包括TP53，ERBB2和PIK3CA在内的各种基因的突变率在年轻患者（≤35岁）中是不同的。我们队列中的三阴性或浸润性小叶BC高于TCGA队列。
■这项研究揭示了中国患者早期BC的各种分子亚型的不同突变特征。此外，我们为东西方早期公元前的差异提供了新的见解。
使用由520个癌症相关基因组成的商业基因组对589例中国早期BC患者的肿瘤和匹配的血液样本进行测序，以分析所有类型的基因组改变并估计TMB状态。
■发现在T3-4期肿瘤中，与T1-2期肿瘤相比，共有18个基因更频繁地突变（P<0.05）或扩增（P<0.05）。发现有淋巴结转移的患者与无淋巴结转移的患者相比，共有18个基因发生了差异突变（P<0.05）或扩增（P<0.05）。年龄较小的患者（≤35岁）在11个基因中发现突变或基因扩增的频率更高（P<0.05）。在我们队列的5.7%中发现TMB>10突变/Mb。尽管在我们的队列和癌症基因组图谱（TCGA）研究的BC队列之间，各种分子亚型的TMB相似，HR+/HER-的TMB有统计学差异，HR+/HER2+,在TCGA研究中，我们的队列与非裔美国人之间存在三阴性亚型。与TCGABC队列相比，我们的队列诊断的中位年龄要早得多(48岁vs.58年,P<0.001)，并且三阴性亚型的频率明显较低(11.5%vs.18.4%,P<0.001）和侵袭性小叶BC（2.4%vs.19.0%,P<0.001)。进一步的亚组分析显示，包括TP53，ERBB2和PIK3CA在内的各种基因的突变率在年轻患者（≤35岁）中是不同的。我们队列中的三阴性或浸润性小叶BC高于TCGA队列。
■这项研究揭示了中国患者早期BC的各种分子亚型的不同突变特征。此外，我们为东西方早期公元前的差异提供了新的见解。
