Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast.
Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast.
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乳腺癌转移性侵袭性微乳头状癌中细胞簇的基因组改变和进化
DOI：
10.1038/s41467-021-27794-4
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发表时间：
2022-01-10
影响因子：
16.6
通讯作者：
Fu L
中科院分区：
文献类型：
--
作者：
Shi Q;Shao K;Jia H;Cao B;Li W;Dong S;Liu J;Wu K;Liu M;Liu F;Zhou H;Lv J;Gu F;Li L;Zhu S;Li S;Li G;Fu L
结果对IMPC的体细胞遗传改变进行了综述。我们对17对新鲜冷冻的IMPC肿瘤和正常组织进行WES，以建立IMPC基因组突变谱的概述（临床病理和测序信息见补充数据1，实验流程图见补充图1），达到平均测序深度（即每个碱基测序的次数）超过155次/样本（中位数= 235次，平均值标准误差[SEM]= 37.23）。我们在原发性IMPC中发现了3569个体细胞突变。在排除2231个沉默突变后，仍然存在1338个突变，包括1190个错义突变、80个无义突变、53个剪接位点、14个缺失和1个不间断突变（Supplementary Fig. 2A和Supplementary data 2， IMPC中的非沉默体细胞突变）。变异类型以单核苷酸变异（SNV）为主，最常见的突变事件是C-to-T转变（Supplementary Fig. 2A），这是乳腺癌（Supplementary Fig. 2B）和其他上皮性肿瘤中常见的事件23。平均IMPC肿瘤突变负担（TMB）为2.32，略高于The Cancer Genome Atlas （TCGA）乳腺癌数据集的平均TMB（平均TMB= 1.75）和TCGA亚型PAM50 luminal B乳腺癌数据集的平均TMB（平均TMB= 1.62），但差异无统计学意义（Student’s t检验，P= 0.178和P= 0.108, Supplementary Data 2）。此外，在IMPC中最常见的突变基因是TP53 （24%, 4%）
ResultsAn overview of the somatic genetic alterations in IMPC. We performed WES of 17 pairs of freshly frozen IMPC tumor and normal tissues to establish an overview of the genomic mutation spectrum of IMPC (the clinicopathological and sequencing information is listed in Supplementary Data 1, and the experimental flow chart is depicted in Supplementary Fig. 1), reaching an average sequencing depth (ie, the number of times each base had been sequenced) of more than 155× per sample (median= 235×, standard error of the mean [SEM]= 37.23). We identified 3569 somatic mutations in the primary IMPC. After the exclusion of 2231 silent mutations, 1338 mutations remained, including 1190 missense, 80 nonsense, 53 splice-site, 14 indels, and 1 nonstop mutation (Supplementary Fig. 2A and SupplementaryData 2, non-silent somatic mutations in IMPC). The variant type was dominated by a single-nucleotide variant (SNV), and the most frequent mutation event was a C-to-T transition (Supplementary Fig. 2A), which is a common event in breast cancer (Supplementary Fig. 2B) and other epithelial tumors 23. The mean IMPC tumor mutation burden (TMB) was 2.32, which was slightly higher than the mean TMBs of The Cancer Genome Atlas (TCGA) breast cancer (mean TMB= 1.75) and TCGA subtype PAM50 luminal B breast cancer datasets (mean TMB= 1.62), but the differences were not significant (Student’s t test, P= 0.178 and P= 0.108, respectively, Supplementary Data 2). Additionally, the most frequently mutated genes in IMPC were TP53 (24%, 4/
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
50.3
作者：
Berger AC;Korkut A;Kanchi RS;Hegde AM;Lenoir W;Liu W;Liu Y;Fan H;Shen H;Ravikumar V;Rao A;Schultz A;Li X;Sumazin P;Williams C;Mestdagh P;Gunaratne PH;Yau C;Bowlby R;Robertson AG;Tiezzi DG;Wang C;Cherniack AD;Godwin AK;Kuderer NM;Rader JS;Zuna RE;Sood AK;Lazar AJ;Ojesina AI;Adebamowo C;Adebamowo SN;Baggerly KA;Chen TW;Chiu HS;Lefever S;Liu L;MacKenzie K;Orsulic S;Roszik J;Shelley CS;Song Q;Vellano CP;Wentzensen N;Cancer Genome Atlas Research Network;Weinstein JN;Mills GB;Levine DA;Akbani R
通讯作者：
Akbani R
影响因子：
4.4
作者：
Hansen, Maria;Walmod, Peter Schledermann
通讯作者：
Walmod, Peter Schledermann
影响因子：
8.4
作者：
FIDLER, IJ
通讯作者：
FIDLER, IJ
影响因子：
3.6
作者：
Chin, Suet-Feung;Santonja, Angela;Caldas, Carlos
通讯作者：
Caldas, Carlos