Genome Evolution Analysis of Recurrent Testicular Malignant Mesothelioma by Whole-Genome Sequencing

Shigeng Zhang; Qi Zhang; Qing Sun; Jinlong Tang; Jimin Chen; Na Ji; Yichun Zheng; Francia Fang; Wanjun Lei; Pengpeng Li; Nan Zhang

doi:10.1159/000486355

Genome Evolution Analysis of Recurrent Testicular Malignant Mesothelioma by Whole-Genome Sequencing

Cell Physiol Biochem. 2018;45(1):163-174. doi: 10.1159/000486355. Epub 2018 Jan 15.

Authors

Shigeng Zhang¹, Qi Zhang², Qing Sun³, Jinlong Tang⁴, Jimin Chen¹, Na Ji⁵, Yichun Zheng¹, Francia Fang⁶, Wanjun Lei⁷, Pengpeng Li⁷, Nan Zhang¹

Affiliations

¹ Department of Surgical Urology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ Department of Nutrient, Affiliated Hospital of Jilin Medical University, Jilin, China.
⁴ Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁵ Department of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁶ Trinity College of Arts and Sciences, Duke University, Durham, North Carolina, USA.
⁷ Beijing Novogene Bioinformatics Technology Co., Ltd, Beijing, China.

PMID: 29334678
DOI: 10.1159/000486355

Abstract

Background/aims: Malignant mesothelioma of the tunica vaginalis testis is a rare and lethal disease. The genomic characteristics and genetic changes of tumor cells during the progression of this disease are unknown.

Methods: we performed whole-genome sequencing of four successive tumor samples derived from surgery and a blood sample in a single patient.

Results: All tumors were found to have significant C-to-T and T-to-C mutations, and amplification of copy number in chromosomes 1 and 12 were notified in all tumor samples. Subclone analysis revealed a parallel evolution of the tumor in this patient. We also identified some mutations in mesothelioma-associated genes such as KIF25, AHNAK, and PRDM2.

Conclusions: The results showed a comprehensive genomic change in malignant mesothelioma of the tunica vaginalis testis and provide a better understanding of the clonal evolution during tumor recurrence and metastasis.

Keywords: Clonal evolution; Mutational landscape; Tumor heterogeneity; Tunica vaginalis testis; Whole-genome sequencing.

MeSH terms

Aged
Antineoplastic Agents / therapeutic use
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics
Evolution, Molecular*
Histone-Lysine N-Methyltransferase / chemistry
Histone-Lysine N-Methyltransferase / genetics
Humans
INDEL Mutation
Kinesins / chemistry
Kinesins / genetics
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Lung Neoplasms / pathology
Lung Neoplasms / radiotherapy
Male
Membrane Proteins / chemistry
Membrane Proteins / genetics
Mesothelioma / drug therapy
Mesothelioma / genetics*
Mesothelioma / pathology
Mesothelioma / radiotherapy
Mesothelioma, Malignant
Mutagenesis, Insertional
Neoplasm Proteins / chemistry
Neoplasm Proteins / genetics
Neoplasm Recurrence, Local
Nuclear Proteins / chemistry
Nuclear Proteins / genetics
Polymorphism, Single Nucleotide
Radiation, Ionizing
Sequence Analysis, DNA
Testicular Neoplasms / genetics*
Testicular Neoplasms / pathology
Transcription Factors / chemistry
Transcription Factors / genetics
Whole Genome Sequencing

Substances

AHNAK protein, human
Antineoplastic Agents
DNA-Binding Proteins
KIF25 protein, human
Membrane Proteins
Neoplasm Proteins
Nuclear Proteins
Transcription Factors
Histone-Lysine N-Methyltransferase
PRDM2 protein, human
Kinesins