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Mutation landscape and tumor mutation burden analysis of Chinese patients with pulmonary sarcomatoid carcinomas

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Abstract

Introduction

Pulmonary sarcomatoid carcinoma (PSC) is a group of rare tumors with the presence of both cancerous and sarcoma components in tumor. In this study, we explore their cancer genomic background and the relationship with clinical prognosis.

Materials and methods

A cohort of 32 PSC patients were retrospectively collected from the First People’s Hospital of Changzhou between 2005 and 2016. Targeted next-generation sequencing (NGS) of 416 cancer-relevant genes was performed on 32 PSC tumors.

Results

EGFR (28%), KRAS (22%), and MET (16%) are the most commonly mutated oncogenes, while the top mutated tumor suppressor genes are TP53 (69%) and RB1 (25%). The majority of EGFR mutations are rare mutations, some of which have not been reported before. Moreover, 4 out of 6 MET alterations are exon 14 skipping, far more frequent than in NSCLC. Interestingly, ARID1A was found to be co-mutated with TP53 at all times. The tumor mutation burden (TMB) is ranging from 3.3 to 52.2 per megabase (MB) with a median of 11.7 per MB and 13 patients have more than 20 mutations per MB. Patients mutated in BRCA2, KMT2B, SMARCA4 or TSC2 have significantly higher TMB compared to patients with wide-type genes.

Conclusion

Our study characterizes the genetic background of Chinese PSC patients and demonstrates the importance of involving EGFR rare mutations and MET exon 14 skipping targeted therapies into clinical trials for treating PSC patients. High TMB are seen in about 40.6% Chinese patients with PSC, which could benefit from immune checkpoint inhibitors.

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Acknowledgements

The research was funded by grant from the International Science and Technology Cooperation Project of Changzhou Science and Technology bureau (number CZ20140016).

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Author notes

  1. Xiaohong Liang and Qing Li contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, No.185, Juqian Road, Tianning District, Changzhou City, Jiangsu Province, People’s Republic of China

    Xiaohong Liang, Song Hu, Yan Li, Yun Zong, Sujuan Zhang & Chong Li

  2. Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China

    Qing Li

  3. Cancer Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China

    Bin Xu

  4. Department of Thoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China

    Qianyun Wang

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  1. Xiaohong Liang
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  2. Qing Li
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  3. Bin Xu
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  4. Song Hu
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  6. Yan Li
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  9. Chong Li
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Correspondence to Chong Li.

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Liang, X., Li, Q., Xu, B. et al. Mutation landscape and tumor mutation burden analysis of Chinese patients with pulmonary sarcomatoid carcinomas. Int J Clin Oncol 24, 1061–1068 (2019). https://doi.org/10.1007/s10147-019-01454-6

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  • DOI: https://doi.org/10.1007/s10147-019-01454-6

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