Comprehensive Molecular Profiling of Colorectal Cancer With Situs Inversus Totalis by Next-Generation Sequencing

Hongsen Li; Liu Gong; Huanqing Cheng; Huina Wang; Xiaochen Zhang; Chuangzhou Rao; Zhangfa Song; Da Wang; Haizhou Lou; Feng Lou; Shanbo Cao; Hongming Pan; Yong Fang

doi:10.3389/fonc.2022.813253

Comprehensive Molecular Profiling of Colorectal Cancer With Situs Inversus Totalis by Next-Generation Sequencing

Front Oncol. 2022 Apr 20:12:813253. doi: 10.3389/fonc.2022.813253. eCollection 2022.

Authors

Hongsen Li¹, Liu Gong¹, Huanqing Cheng², Huina Wang³, Xiaochen Zhang⁴, Chuangzhou Rao⁵, Zhangfa Song⁶, Da Wang⁶, Haizhou Lou¹, Feng Lou³, Shanbo Cao³, Hongming Pan¹, Yong Fang¹

Affiliations

¹ Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Prenatal Diagnosis Center, Affiliated Hospital of Weifang Medical University, Weifang, China.
³ Acornmed Biotechnology Co., Ltd., Beijing, China.
⁴ Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁵ Department of Radiotherapy and Chemotherapy, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, China.
⁶ Department of Anorectal Surgical, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Background: Colorectal cancer (CRC) is one of the most prevalent malignances worldwide. However, CRC with situs inversus totalis (SCRC) is extremely rare, and molecular characterization of this disease has never been investigated.

Methods: Tumor tissue samples from 8 patients with SCRC and 33 CRC patients without situs inversus totalis (NSCRC) were subjected to multigene next-generation sequencing.

Results: The most frequently mutated genes in SCRC were APC, TP53, CHEK2, MDC1, GNAQ, KRAS, and SMAD4. A high frequency of SCRC tumors had mutations in DNA damage repair genes. Single amino acid substitutions in the DNA damage repair genes caused by continuous double base substitution was identified in the majority of this population. Furthermore, mutational profiles showed notable differences between the SCRC and NSCRC groups. In particular, CHEK2, MDC1, GNAQ, SMAD4, BRCA1, HLA-B, LATS2, and NLRC5 mutations were more frequently observed in SCRC patients. The mutation loci distributions of KRAS in the SCRC cohort differed from that of the NSCRC cohort. Additionally, differences in the targeted genomic profiles and base substitution patterns were observed between the two groups.

Conclusions: These findings comprehensively revealed a molecular characterization of SCRC, which will contribute to the development of personalized therapy and improved clinical management of SCRC patients.

Keywords: NSCRC; SCRC; colorectal cancer; mutational profile; next-generation sequencing.