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<p>Colorectal cancer (CRC) is a high-incidence malignancy that could be found a as a part of multiple primary cancers (MPCs). Although molecular mechanisms of MPCs have been widely discussed, they are not fully understood. The aim of this study was to investigate clinical and genetic characteristics of MPCs colorectal component in Russian cohort patients. 512 CRC patients were included (62 with synchronous and/or metachronous MPCs). DNA was isolated from paraffin-embedded tissues, <i>KRAS</i>, <i>NRAS</i>, <i>BRAF</i> mutations and MSI status were analyzed, and targeted high-throughput sequencing was performed. Results were analyzed using bioinformatics tools to detect different genetic changes. No significant differences were observed between MPCs and single CRC (sCRC) in terms of gender, age, and histological type. Mucinous adenocarcinoma was more frequent in MPCs patients younger than 45 years, but in elderly sCRC patients. Neoplasms in the transverse colon were significantly higher in MPCs (<i>p</i> = 0.004) and rectum malignancies were mainly registered in sCRC (<i>p</i> = 0.005). The frequency of <i>KRAS</i> (G12A) and MSI-H were significantly higher in MPCs compared to sCRC group (<i>p</i> &lt; 0.0001 and <i>p</i> = 0.04, respectively). CRC samples of MPCs showed predominantly missense mutations (51.9%) and nonsense mutations (42.3%) in 16 out of 32 analyzed genes, mainly <i>TP53</i>, <i>KRAS</i>, <i>PIK3CA</i>,<i> APC</i> and <i>BRAF</i>. Mutational profile of these samples identified alterations in RTK-RAS, WNT, TP53 and PI3K signaling pathways. Studying CRC morphological and genetic features in MPCs patients will expand the understanding of molecular genetic mechanisms of multiple cancers to improve treatment strategies and prognosis.</p>

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Clinico-Morphological and Genetic Features of Colorectal Cancer in Multiple Primary Cancers Cases

  • 期刊论文

  • 发表日期：

    2026年2月16日

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  • Natalya N. Timoshkina,
  • Dmitry Yu. Gvaldin,
  • Dema Alset,
  • Inna A. Novikova,
  • Oleg I. Kit

摘要

Colorectal cancer (CRC) is a high-incidence malignancy that could be found a as a part of multiple primary cancers (MPCs). Although molecular mechanisms of MPCs have been widely discussed, they are not fully understood. The aim of this study was to investigate clinical and genetic characteristics of MPCs colorectal component in Russian cohort patients. 512 CRC patients were included (62 with synchronous and/or metachronous MPCs). DNA was isolated from paraffin-embedded tissues, KRAS, NRAS, BRAF mutations and MSI status were analyzed, and targeted high-throughput sequencing was performed. Results were analyzed using bioinformatics tools to detect different genetic changes. No significant differences were observed between MPCs and single CRC (sCRC) in terms of gender, age, and histological type. Mucinous adenocarcinoma was more frequent in MPCs patients younger than 45 years, but in elderly sCRC patients. Neoplasms in the transverse colon were significantly higher in MPCs (p = 0.004) and rectum malignancies were mainly registered in sCRC (p = 0.005). The frequency of KRAS (G12A) and MSI-H were significantly higher in MPCs compared to sCRC group (p < 0.0001 and p = 0.04, respectively). CRC samples of MPCs showed predominantly missense mutations (51.9%) and nonsense mutations (42.3%) in 16 out of 32 analyzed genes, mainly TP53, KRAS, PIK3CA, APC and BRAF. Mutational profile of these samples identified alterations in RTK-RAS, WNT, TP53 and PI3K signaling pathways. Studying CRC morphological and genetic features in MPCs patients will expand the understanding of molecular genetic mechanisms of multiple cancers to improve treatment strategies and prognosis.