Association between a single nucleotide polymorphism in the <i>R3HCC1</i> gene and irinotecan toxicity

Kanesada, Kou; Tsunedomi, Ryouichi; Hazama, Shoichi; Ogihara, Hiroyuki; Hamamoto, Yoshihiko; Shindo, Yoshitaro; Matsui, Hiroto; Tokumitsu, Yukio; Yoshida, Shigeo; Iida, Michihisa; Suzuki, Nobuaki; Takeda, Shigeru; Ioka, Tatsuya; Nagano, Hiroaki

doi:10.1002/cam4.5299

Cited by 3 publications

(1 citation statement)

References 55 publications

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“…Whole exome sequencing (WES) was performed using DNA from peripheral blood and tumors as previously described [11]. WES revealed germline mutations in PMS2 (rs2228006, c.1621A > G), PMS2 (rs1805321, c.1408C > T), and MSH2 (rs63750716, c.505A > G), which were not pathogenic.…”

Section: Case Presentationmentioning

confidence: 99%

Juvenile colon cancer diagnosed by onset of intussusception: a case report suggestive of Lynch syndrome treated with laparoscopic colectomy

Ogata¹,

Fujii²,

Hino³

et al. 2023

Preprint

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Background: One characteristic of Lynch syndrome, which is caused by germline mutations in a group of genes encoding mismatch repair proteins, is the early onset of colorectal cancer. Here, we report a rare case of juvenile colon cancer, diagnosed based on the onset of intussusception with high microsatellite instability (MSI) and the absence of BRAF mutations, which was suggestive of Lynch syndrome. Case presentation: A 28-year-oldman presented with right lower abdominal pain for approximately 3 months and defecated blacky stool for several weeks. He visited our hospital because of increasingly intense right lower abdominal pain. Computed tomography revealed a contrast-enhanced tumor and lymph nodes with a crab-claw-like fitted image extending into the ascending colon. Colon endoscopy revealed a large submucosal tumor-like lesion with ulceration. Laparoscopy-assisted ileal resection with level 3 lymph node dissection was performed 3 days after the endoscopic reduction of the intussusception. The histological diagnosis was a poorly differentiated adenocarcinoma. Gene analysis of the resected tumor revealed high MSIand KRAS mutations, and the absence of BRAF mutations. Immunohistochemistry indicated the absence of MLH1 and PMS2 expression in tumors. Genetic analysis of peripheral blood and tumors revealed no pathological mutations in MLH1, MSH2, PMS2, or MSH6. Conclusion A rare case of Lynch-like syndrome was diagnosed with intussusception. MSI-high, wild-type BRAF, and the absence of MLH1 and PMS2 expression suggested Lynch syndrome. The absence of pathological mutations in germline and somatic genes suggests the possibility of MLH1 promoter methylation or MLH1 epimutation in the pathogenesis of this case.

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Section: Case Presentationmentioning

confidence: 99%

Juvenile colon cancer diagnosed by onset of intussusception: a case report suggestive of Lynch syndrome treated with laparoscopic colectomy

Ogata¹,

Fujii²,

Hino³

et al. 2023

Preprint

Self Cite

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Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity

et al. 2022

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Objective: Irinotecan is a useful anticancer drug for colorectal cancer treatment. UGT1A1*28 and *6 gene polymorphisms are known risk factors for irinotecanassociated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than UGT1A.Methods: A total of 178 patients with metastatic colorectal cancer (mCRC) and 87 patients with pancreatic cancer were treated with FOLFIRI, FOLFOX, FOLFOXIRI, modified FOLFIRINOX, or gemcitabine plus nab-paclitaxel.Genome-wide screening was performed using whole-exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe.Results: Using WES after a doublet chemotherapy regimen comprising irinotecan and 5-fluorouracil (n = 15), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan-associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled-coil containing 1 (R3HCC1; c.919G > A, rs2272761) showed a significant association with neutropenia (>grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (n = 23) or modified FOLFIRINOX for pancreatic cancer (n = 40), also showed significant linear trends between R3HCC1 polymorphism and neutropenia (p = 0.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan-free regimens, FOLFOX for mCRC (n = 66), and gemcitabine plus nab-paclitaxel for pancreatic cancer (n = 47). Conclusion:Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer.

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The tumor immune microenvironment in pancreatic cancer and its potential in the identification of immunotherapy biomarkers

Tsunedomi,

Shindo,

Nakajima

et al. 2023

Expert Review of Molecular Diagnostics

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Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity

Cited by 3 publications

References 55 publications

Juvenile colon cancer diagnosed by onset of intussusception: a case report suggestive of Lynch syndrome treated with laparoscopic colectomy

Juvenile colon cancer diagnosed by onset of intussusception: a case report suggestive of Lynch syndrome treated with laparoscopic colectomy

Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity

The tumor immune microenvironment in pancreatic cancer and its potential in the identification of immunotherapy biomarkers

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