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

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

Hongsen Li  1 , Liu Gong  1 , Huanqing Cheng  2 , Huina Wang  3 , Xiaochen Zhang  4 , Chuangzhou Rao  5 , Zhangfa Song  6 , Da Wang  6 , Haizhou Lou  1 , Feng Lou  3 , Shanbo Cao  3 , Hongming Pan  1 , Yong Fang  1
Affiliations

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

Hongsen Li et al. Front Oncol. .

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.

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Conflict of interest statement

HW, FL, and SC are employees of Acornmed Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mutational landscape of colorectal cancer patients with situs inversus totalis (SCRC). Genomic mutations were identified by targeted NGS of the tumor tissues from patients with SCRC. Multiple mutations, mutations numbers greater than two.
Figure 2
Figure 2
Transition (Ti) and transversion (Tv) profiles for SCRC. (A) Comparison between Ti and Tv ratios in SCRC. (B) The bar plot shows each type of Ti or Tv. (C) The box plot exhibits the ratio of each type of Ti or Tv for each patient.
Figure 3
Figure 3
Comparison of the genomic landscape between SCRC and NSCRC cohorts. (A) Frequencies of genomic mutations in SCRC and NSCRC cohorts. (B) Corresponding P values comparing the prevalence of a gene’s mutations between different cohorts. Cases with a statistically significant difference (P < 0.05) are highlighted in yellow.
Figure 4
Figure 4
The mutation loci distributions of KRAS in SCRC and NSCRC groups. (A) Distributions of KRAS mutations identified in SCRC. (B) Distribution of KRAS mutations identified in NSCRC. (C) Comparison of the distributions of KRAS mutations between SCRC and NSCRC patients.
Figure 5
Figure 5
Comparison of the profiles of transition (Ti) and transversion (Tv) between SCRC and NSCRC patients. (A) The bar plot shows each type of Ti or Tv in NSCRC. (B) Comparison between Ti and Tv ratios in NSCRC. (C) Comparison of Ti ratios between the SCRC and NSCRC groups.
Figure 6
Figure 6
Comparison between SCRC and NSCRC patients of the detection rate of genomic mutations in signaling pathways.
Figure 7
Figure 7
Comparison of the DDR profiles between SCRC and NSCRC patients. (A) The DDR profile in the SCRC group. (B) The DDR profile in the NSCRC group.
Figure 8
Figure 8
Comparison of the targeted genomic profiles between CRC and NSCRC patients. (A) The targeted genomic profile in the SCRC group. (B) The targeted genomic profile in the NSCRC group.
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