Case Report: A germline SDHB c.268C>T (p.Arg90Ter) variant in a family with very-early-onset colorectal neoplasia
- 1Day Surgery Center, The First Affiliated Hospital of Kunming Medical University
- 2Surgical Oncology, The First Affiliated Hospital of Kunming Medical University
Abstract
Background: Very-early-onset colorectal cancer (CRC), particularly when clustered within a family, raises concern for an inherited cancer predisposition. However, the contribution of germline SDHB variants to CRC susceptibility remains uncertain. We report a family in which two sisters developed colorectal carcinoma before 25 years of age and in whom a known pathogenic germline SDHB variant was identified.
Case presentation: A 22-year-old woman presented with a 3-year history of intermittent hematochezia. Complete colonoscopy identified an ulcerated lesion in the rectosigmoid region approximately 15 cm from the anal verge. Endoscopic biopsy showed high-grade intraepithelial neoplasia with focal intramucosal carcinoma. The patient underwent laparoscopic rectal resection with lymph-node dissection and sigmoidorectal anastomosis. The surgical resection specimen demonstrated moderately differentiated adenocarcinoma, pT3N0M0, stage IIA, with no metastatic involvement in 14 examined lymph nodes. Germline testing identified SDHB NM_003000.3:c.268C>T (p.Arg90Ter). Her elder sister had developed rectal adenocarcinoma at 19 years of age, whereas their father had two rectal polyps measuring approximately 0.6 and 0.8 cm, with histopathology demonstrating tubular adenoma. The same germline SDHB variant was detected in the proband, her elder sister, and her father. In the proband’s tumor, the SDHB variant showed a VAF of 20.75%, SDHB protein expression was retained, and no biallelic SDHB inactivation was demonstrated. The tumor additionally harbored a somatic TP53 frameshift alteration and SMAD4 copy-number loss.
Conclusions: This family demonstrates remarkable clustering of very-early-onset colorectal neoplasia together with a known pathogenic germline SDHB variant. However, the available segregation, molecular, and immunohistochemical evidence is insufficient to establish SDHB as a CRC susceptibility gene or to demonstrate an SDHB -driven tumor mechanism. This observation should therefore be considered hypothesis-generating and warrants validation in additional families, larger cohorts, comprehensive genomic analyses, and CRC-specific functional studies.
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BibTeX
@article{liu2026case,
title = {{Case Report: A germline SDHB c.268C>T (p.Arg90Ter) variant in a family with very-early-onset colorectal neoplasia}},
author = {Chang Liu and Dayang Zhou and Wenjing Xu and Hai Pan and Xiang Ji and Jian Huang and Zhu Zhu},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1938314},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1938314/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: A germline SDHB c.268C>T (p.Arg90Ter) variant in a family with very-early-onset colorectal neoplasia
AU - Chang Liu
AU - Dayang Zhou
AU - Wenjing Xu
AU - Hai Pan
AU - Xiang Ji
AU - Jian Huang
AU - Zhu Zhu
PY - 2026
DA - 2026/10/16
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1938314
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1938314/full
AB - Background: Very-early-onset colorectal cancer (CRC), particularly when clustered within a family, raises concern for an inherited cancer predisposition. However, the contribution of germline SDHB variants to CRC susceptibility remains uncertain. We report a family in which two sisters developed colorectal carcinoma before 25 years of age and in whom a known pathogenic germline SDHB variant was identified. Case presentation: A 22-year-old woman presented with a 3-year history of intermittent hematochezia. Complete colonoscopy identified an ulcerated lesion in the rectosigmoid region approximately 15 cm from the anal verge. Endoscopic biopsy showed high-grade intraepithelial neoplasia with focal intramucosal carcinoma. The patient underwent laparoscopic rectal resection with lymph-node dissection and sigmoidorectal anastomosis. The surgical resection specimen demonstrated moderately differentiated adenocarcinoma, pT3N0M0, stage IIA, with no metastatic involvement in 14 examined lymph nodes. Germline testing identified SDHB NM_003000.3:c.268C>T (p.Arg90Ter). Her elder sister had developed rectal adenocarcinoma at 19 years of age, whereas their father had two rectal polyps measuring approximately 0.6 and 0.8 cm, with histopathology demonstrating tubular adenoma. The same germline SDHB variant was detected in the proband, her elder sister, and her father. In the proband’s tumor, the SDHB variant showed a VAF of 20.75%, SDHB protein expression was retained, and no biallelic SDHB inactivation was demonstrated. The tumor additionally harbored a somatic TP53 frameshift alteration and SMAD4 copy-number loss. Conclusions: This family demonstrates remarkable clustering of very-early-onset colorectal neoplasia together with a known pathogenic germline SDHB variant. However, the available segregation, molecular, and immunohistochemical evidence is insufficient to establish SDHB as a CRC susceptibility gene or to demonstrate an SDHB -driven tumor mechanism. This observation should therefore be considered hypothesis-generating and warrants validation in additional families, larger cohorts, comprehensive genomic analyses, and CRC-specific functional studies.
SN - 2234-943X
ER -