Mutational concordance analysis provides supportive information for double cancer diagnosis

BMC Cancer

Yuji Shimoda¹  Sumiko Ohnami¹  Shumpei Ohnami¹  Takeshi Nagashima¹  Kenichi Urakami¹  Akifumi Notsu²  Hirotsugu Kenmotsu³  Akane Naruoka⁴  Koji Maruyama⁵  Tadashi Ashizawa⁶  Yasuto Akiyama⁶  Akira Iizuka⁶  Tohru Mochizuki⁷  Keiichi Hatakeyama⁷  Keiichi Ohshima⁷  Ken Yamaguchi⁸ 

[1] Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute;Clinical Research Center, Shizuoka Cancer Center;Division of Genetic Medicine Promotion, Shizuoka Cancer Center;Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute;Experimental Animal Facility, Shizuoka Cancer Center Research Institute;Immunotheraphy Division, Shizuoka Cancer Center Research Institute;Medical Genetics Division, Shizuoka Cancer Center Research Institute;Shizuoka Cancer Center;

关键词: Whole exome sequencing;    Double cancer;    Tumor mutational burden;    Poisson distribution;   

DOI  :  10.1186/s12885-021-07899-1

来源: DOAJ

【 摘 要 】

Abstract Background Mutation analysis using next-generation sequencing highlights the features of tumors with somatic alterations. However, the mutation profile of double cancer remains unclear. Here, we analyzed tumors derived from the same patient using whole exome sequencing (WES) to investigate the coherence of somatic mutations in double cancer. Methods First, the tumor mutational burden (TMB) was investigated using WES of 5521 tumor specimens from a Japanese pan-cancer cohort. The frequencies of mutation concordance were then compared in these cancers. Finally, we calculated the expected value of mutational concordance fitting a Poisson distribution to determine the relationship between double and metastatic cancers. Results In all, 44, 58, and 121 paired samples were diagnosed as double cancer, multifocal lesions (derived from identical tissues), and metastasis, respectively. Our analysis revealed that common somatic mutations were almost entirely absent in double cancer, whereas primary tumors and metastatic foci harbored several identical alterations. Concordance of the mutation profile in the same patient reflects the tumor origin and development, suggesting the potential for identifying double cancer based on common somatic mutations. Furthermore, according to a Poisson distribution, double cancer could be discriminated based on paired samples from the same patient. The probability of double cancer with more than 10 mutations was ≤1 part-per-billion (ppb, 10− 9). In multifocal lesions, 74% of tumor pairs accumulated ≤10 common mutations, implying a difference in tumor origin within identical tissues. Conclusions These findings indicate that counting common somatic mutations can indicate the differences in origin between tumors derived from the same patient. Our mutation coherence analysis can thus provide beneficial information for diagnosing double cancer.

【 授权许可】

Unknown