Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing

Kan Li; Jianbin Gong; Qiuhan Zheng; Le Yang; Xueying Mei; Jianghai Chen; Guiqing Liao; Yujie Liang

doi:10.3389/fonc.2022.971546

Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing

Front Oncol. 2022 Oct 20:12:971546. doi: 10.3389/fonc.2022.971546. eCollection 2022.

Authors

Kan Li^{1

2

3}, Jianbin Gong^{1

2

3}, Qiuhan Zheng^{1

2

3}, Le Yang^{1

2

3}, Xueying Mei^{1

2

3}, Jianghai Chen^{1

2

3}, Guiqing Liao^{1

2

3}, Yujie Liang^{1

2

3}

Affiliations

¹ Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
³ Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.

Abstract

Multiple primary cancers (MPCs) refer to cancers that occur simultaneously or metachronously in the same individual. The incidence of MPC has increased recently, as the survival time of malignant tumor patients has been greatly prolonged. It is difficult to differentiate MPC from primary cancers (PCs) in the same anatomical region from the clinical manifestation alone. However, their biological behaviors appear to be distinct. In this study, we show that the prognosis of multiple primary oral cancers (MP-OCs) is worse than primary oral cancers (P-OCs). To better understand the molecular mechanisms of MP-OC, we used whole exome sequencing (WES) to analyze samples from 9 patients with MP-OC and 21 patients with P-OC. We found more somatic mutations in MP-OC than in P-OC. MP-OC had more complicated mutation signatures, which were associated with age-related and Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) activity-related signatures. Tumor mutational burden (TMB) and mutant-allele tumor heterogeneity (MATH) of MP-OC trended higher compared to P-OC. KEGG and GO analysis showed the differential pathways of MP-OC versus P-OC. In addition, MP-OC took amplification, not loss, as the main pattern of copy number variation (CNV), while P-OC took both. Lastly, we did not find significantly different mutant germline genes, but MSH-6 mutation may be a potential MP-OC driver. In short, our preliminary results show that MP-OC and P-OC have different molecular characteristics.

Keywords: copy number variation; germline mutation; multiple primary oral cancer; mutational signatures; whole exon sequencing.