Whole exome sequencing in Chinese mucinous pulmonary adenocarcinoma uncovers specific genetic variations different from lung adenocarcinoma

Chenyue Zhang; Kai Wang; Wenjie Liu; Jiamao Lin; Zhenxiang Li; Hui Wang; Chenglong Zhao; Yanhua Chen; Shuangxiu Wu; Airong Yang; Jiayan Wu; Haiyong Wang

doi:10.3389/fonc.2022.1054845

Whole exome sequencing in Chinese mucinous pulmonary adenocarcinoma uncovers specific genetic variations different from lung adenocarcinoma

Front Oncol. 2022 Dec 15:12:1054845. doi: 10.3389/fonc.2022.1054845. eCollection 2022.

Authors

Chenyue Zhang¹, Kai Wang², Wenjie Liu³, Jiamao Lin⁴, Zhenxiang Li⁵, Hui Wang⁶, Chenglong Zhao⁷, Yanhua Chen⁸, Shuangxiu Wu³, Airong Yang⁸, Jiayan Wu³, Haiyong Wang⁹

Affiliations

¹ Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, China.
² Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China.
³ Research Institute, Berry Oncology Corporation, Beijing, China.
⁴ Department of Traditional Chinese medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
⁵ Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
⁶ Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁷ Department of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China.
⁸ Department of Biological Information, Berry Oncology Corporation, Beijing, China.
⁹ Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Abstract

Background: As a rare subtype of primary lung adenocarcinoma (LUAD), mucinous pulmonary adenocarcinoma (MPA) was considered a distinctive entity with unfavorable outcomes. Therefore, there is a great need for a better understanding of the genomic and immunological landscape of this rare tumor type, which would inform improved therapeutic strategies.

Methods: A total of 96 patients histologically confirmed with MPA were recruited from Shandong Cancer Hospital and Institute (SCH). Single nucleotide variation (SNV), copy number variation (CNV), genomic instability, and immunological landscape insights into 96 MPA patients were identified using WES.

Results: We demonstrated that MPAs had marked different genomic alterations and were more complex in genomic profiles than LUADs. Mutations in Tumor Protein 53 (TP53) and CYP7A Promoter-Binding Factor (CPF) pathways significantly shortened survival whereas mutations in Notch and Wnt pathways significantly prolonged survival in MPA. Besides, we demonstrated that mutations in immune-related genes influenced outcomes, with mutations in TP53, Ataxia Telangiectasia Mutated (ATM), Polymerase (DNA) Delta 1 (POLD1), and Epidermal Growth Factor Receptor (EGFR) correlated with worsened survival.

Conclusions: We not only depicted the genetic and immunologic landscape of Chinese MPA but also reveal its distinction from LUAD in genomic and immune context. Our findings may provide opportunities for therapeutic susceptibility among Chinese MPA patients.

Keywords: genomics; immunological features; mucinous pulmonary adenocarcinoma; therapeutics; whole exome sequencing.