TCGA的肿瘤突变负荷

不论你是做TCGA数据挖掘,还是自己的研究结果与TCGA数据库比较,都需要掌握一定的TCGA数据处理方法。当然,很多公众号都有TCGA数据挖掘的讲解,这里就不做赘述了。

什么是TMB?

如果你从事肿瘤相关研究,那么对Tumor mutation burden(TMB)一定不陌生,是指每Mb上产生的非同义突变的数目,产生的突变数目越多,意味着可能产生更多的新抗原,即越有可能被免疫系统识别,对免疫治疗敏感。TMB可以作为免疫治疗疗效的潜在指标,小编在文末整理了几篇经典的文献供大家学习。

如何计算TCGA全外显子突变数据的TMB?

计算TCGA数据(WES)的TMB,目前主要有两种方式:

1. 直接用非同义突变的数目来代表肿瘤的突变负荷。适用于同一批WES数据不同分组的TMB比较。

(Tips:  除了TCGA的全外显子数据外,任何全外显子数据都可以这样来计算TMB)

2. 非同义突变数目除以外显子芯片大小。TCGA全外显子芯片大小约38Mb。适用于不同研究间的TMB比较。

(Tips.非TCGA的WES数据,要根据实际芯片大小的情况作为分母,计算每Mb下产生了多少个非同义突变)

参考文献:

1.Rosenberg, J. E. et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387, 1909–1920 (2016).

2.Seiwert, T. Y. et al. Biomarkers predictive of response to pembrolizumab in head and neck cancer (HNSCC). Cancer Res. 73, LB–339 (2018).

3.Hellmann, M. D. et al. Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer. Cancer Cell 33, 843–852 e844 (2018).

4.Rizvi, H.et al. Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profled with targeted next-generation sequencing. J. Clin. Oncol. 36, 633–641 2018).

5.Hellmann, M. D. et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N. Engl. J. Med. 378, 2093–2104 (2018).

6.Carbone, D. P. et al. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N. Engl. J. Med. 376, 2415–2426 (2017).

7.Hellmann, M. D. et al. Tumor mutational burden and efcacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell 33, 853–861 e854 (2018).

8.Hellmann, Matthew D., et al. “Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer.” Cancer Cell 33.5 (2018): 843-852.

9.Chalmers, Zachary R., et al. “Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden.” Genome medicine 9.1 (2017): 34.

杂谈

TCGA中的致癌信号通路

2020-8-28 0:50:28

杂谈

评估肿瘤纯度的方法(二):基于单核苷酸变异 TPES

2020-8-28 1:20:41

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