Scholarlink

<p>Colorectal cancer (CRC) is increasingly diagnosed in individuals under 50 years of age, yet the underlying genetic predisposition remains largely unexplained, particularly in mismatch repair (MMR)-proficient cases. This study aimed to identify novel hereditary CRC susceptibility genes by integrating germline and tumour whole-exome sequencing (WES) with transcriptomic profiling across a cohort of early-onset CRC (EOCRC) patients. Tumours were categorised using Consensus Molecular Subtypes (CMS) classification and analysed for mutational signature and burden. We used a novel ‘All vs One’ multi-omic integration approach to identify loss-of-function rare germline variants with concordant gene expression alterations in tumour tissue. Five candidate genes (<i>ADCY4</i>, <i>NOXO1, CDHR2</i>, <i>ARHGAP10</i>, <i>EEF2K</i>) were prioritised based on this approach and potential biological relevance in CRC. These findings highlight the molecular heterogeneity of EOCRC and demonstrate the utility of multi-omic approaches in refining germline variant interpretation. Integrating tumour transcriptomics enhances gene discovery efforts and supports a more comprehensive understanding of CRC heritability in younger individuals.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Integration of multi-omics data uncovers novel germline susceptibility candidates in early-onset colorectal cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月15日

查看全文
  • Anael López-Novo,
  • Jorge Amigo,
  • Andrés Dacal,
  • David Remedios-Espino,
  • Joaquín Cubiella,
  • María Victoria Álvarez-Sánchez,
  • María Jesús Ladra-González,
  • Fernando Fernández-López,
  • Ana Álvarez-Castro,
  • Silvia Carlés,
  • José Manuel Cameselle-Teijeiro,
  • Miriam Cuatrecasas,
  • Francesc Balaguer,
  • Sergi Castellví-Bel,
  • Ceres Fernández-Rozadilla,
  • Ángel Carracedo,
  • Clara Ruiz-Ponte

摘要

Colorectal cancer (CRC) is increasingly diagnosed in individuals under 50 years of age, yet the underlying genetic predisposition remains largely unexplained, particularly in mismatch repair (MMR)-proficient cases. This study aimed to identify novel hereditary CRC susceptibility genes by integrating germline and tumour whole-exome sequencing (WES) with transcriptomic profiling across a cohort of early-onset CRC (EOCRC) patients. Tumours were categorised using Consensus Molecular Subtypes (CMS) classification and analysed for mutational signature and burden. We used a novel ‘All vs One’ multi-omic integration approach to identify loss-of-function rare germline variants with concordant gene expression alterations in tumour tissue. Five candidate genes (ADCY4, NOXO1, CDHR2, ARHGAP10, EEF2K) were prioritised based on this approach and potential biological relevance in CRC. These findings highlight the molecular heterogeneity of EOCRC and demonstrate the utility of multi-omic approaches in refining germline variant interpretation. Integrating tumour transcriptomics enhances gene discovery efforts and supports a more comprehensive understanding of CRC heritability in younger individuals.