Annals of surgical oncology · 2026
Extrachromosomal Circular DNA May Contribute to Histopathologic Characteristics in Esophageal Combined Basaloid Squamous Cell Carcinoma.
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Kuriyama Kengo, Erkhem-Ochir Bilguun, Tagami Michihira, Sohda Makoto, Nakazawa Nobuhiro, Sano Akihiko, Sakai Makoto, Kawabata-Iwakawa Reika, Manabe Ri-Ichiroh, Kuwano Hiroyuki, Yao Takashi, Shirabe Ken, Yokobori Takehiko, Saeki Hiroshi
Аннотация
BACKGROUND: Combined basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare cancer comprising basaloid and esophageal squamous cell carcinoma (ESCC) components. The origin of each component in combined BSCC remains unknown. This study aimed to determine whether combined BSCC originated from BSCC or ESCC.
METHODS: In this study, whole-genome sequencing (WGS) was performed using laser-microdissected samples from BSCC and ESCC components separately from the primary lesions of patients with combined BSCC.
RESULTS: Whole-genome sequencing (WGS) of laser-microdissected samples from three combined BSCCs showed the characteristic copy number gain of Chr7, including the EGFR gene, in only the ESCC but not the non-cancerous and BSCC components in two cases. Moreover, the amplified Chr7 region was validated through EGFR gene fluorescence in situ hybridization and was suggested to form extrachromosomal circular DNA (eccDNA) based on the presence of boundary sequences that do not map on the human genome. The boundary and EGFR sequences on eccDNA were detected only in the ESCC components using polymerase chain reaction-based analyses after linear DNA structure-specific-restriction enzyme treatment.
CONCLUSION: These findings suggest that eccDNA harboring the EGFR oncogene may contribute to BSCC transformation into ESCC in combined BSCC tumors, exhibiting a novel eccDNA function that causes histologic diversity in mixed carcinomas.
METHODS: In this study, whole-genome sequencing (WGS) was performed using laser-microdissected samples from BSCC and ESCC components separately from the primary lesions of patients with combined BSCC.
RESULTS: Whole-genome sequencing (WGS) of laser-microdissected samples from three combined BSCCs showed the characteristic copy number gain of Chr7, including the EGFR gene, in only the ESCC but not the non-cancerous and BSCC components in two cases. Moreover, the amplified Chr7 region was validated through EGFR gene fluorescence in situ hybridization and was suggested to form extrachromosomal circular DNA (eccDNA) based on the presence of boundary sequences that do not map on the human genome. The boundary and EGFR sequences on eccDNA were detected only in the ESCC components using polymerase chain reaction-based analyses after linear DNA structure-specific-restriction enzyme treatment.
CONCLUSION: These findings suggest that eccDNA harboring the EGFR oncogene may contribute to BSCC transformation into ESCC in combined BSCC tumors, exhibiting a novel eccDNA function that causes histologic diversity in mixed carcinomas.