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<p>Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. Adenomas, precursors to CRC, can be diagnosed early, but the genetic events leading to adenoma–adenocarcinoma conversion remain unclear. This study explored the role of chromosomal instabilities (CINs) in this conversion. Over a 17-year follow-up period, 119 adenomas were analyzed using low-coverage whole-genome sequencing (LC-WGS) and Ultrasensitive Chromosomal Aneuploidy Detector. Risk factors for adenocarcinoma development were identified through logistic regression analysis, and survival was assessed using Kaplan–Meier curves. CIN was found in 32% of adenomas, with a higher incidence in high-grade adenomas (<i>P</i> = 0.0359). Common chromosomal changes included loss of 18q, 1p, and 17p and gain of 8q (MYC), 20q, and 7p (EGFR). During the 17-year follow-up, 88 patients experienced recurrence, including 40 cases of adenomas and 48 cases of progression to adenocarcinoma. CIN was identified in 40% of progression cases, 33.6% of adenoma recurrence cases, and 26% of nonrecurrent cases. A strong genetic linkage was observed before and after tumor transformation, with a high match between the tumors and matched prior adenomas. CIN was significantly associated with disease progression (HR: 2.5, 95% CI: 1.4–4.5, <i>P</i> = 0.00162) and was an independent risk factor. Additionally, MFN2 gene copy number deletion was linked to recurrence and/or progression after resection, with reduced expression in tumor tissues. In conclusion, CIN is a key risk factor for adenoma recurrence and progression, and MFN2 gene copy number deletion is associated with adverse outcomes, providing insights for more accurate clinical prognostication of adenoma-to-adenocarcinoma transformation.</p>

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Tumor associated chromosomal instability drives colorectal adenoma to adenocarcinoma progression based on 17 year follow up evidence

  • 期刊论文

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  • 发表日期：

    2025年4月21日

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  • Hui Li,
  • Fang Yang,
  • Bingjun Bai,
  • Zhinong Jiang,
  • Bing Li,
  • Guoxiang Fu,
  • Xiaotong Hu

摘要

Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. Adenomas, precursors to CRC, can be diagnosed early, but the genetic events leading to adenoma–adenocarcinoma conversion remain unclear. This study explored the role of chromosomal instabilities (CINs) in this conversion. Over a 17-year follow-up period, 119 adenomas were analyzed using low-coverage whole-genome sequencing (LC-WGS) and Ultrasensitive Chromosomal Aneuploidy Detector. Risk factors for adenocarcinoma development were identified through logistic regression analysis, and survival was assessed using Kaplan–Meier curves. CIN was found in 32% of adenomas, with a higher incidence in high-grade adenomas (P = 0.0359). Common chromosomal changes included loss of 18q, 1p, and 17p and gain of 8q (MYC), 20q, and 7p (EGFR). During the 17-year follow-up, 88 patients experienced recurrence, including 40 cases of adenomas and 48 cases of progression to adenocarcinoma. CIN was identified in 40% of progression cases, 33.6% of adenoma recurrence cases, and 26% of nonrecurrent cases. A strong genetic linkage was observed before and after tumor transformation, with a high match between the tumors and matched prior adenomas. CIN was significantly associated with disease progression (HR: 2.5, 95% CI: 1.4–4.5, P = 0.00162) and was an independent risk factor. Additionally, MFN2 gene copy number deletion was linked to recurrence and/or progression after resection, with reduced expression in tumor tissues. In conclusion, CIN is a key risk factor for adenoma recurrence and progression, and MFN2 gene copy number deletion is associated with adverse outcomes, providing insights for more accurate clinical prognostication of adenoma-to-adenocarcinoma transformation.