TP53 mutation status and consensus molecular subtypes of colorectal cancer in patients from Rwanda

Autor: Augustin Nzitakera, Delphine Uwamariya, Hisami Kato, Jean Bosco Surwumwe, André Mbonigaba, Ella Larissa Ndoricyimpaye, Schifra Uwamungu, Felix Manirakiza, Marie Claire Ndayisaba, Gervais Ntakirutimana, Benoit Seminega, Vincent Dusabejambo, Eric Rutaganda, Placide Kamali, François Ngabonziza, Rei Ishikawa, Hirofumi Watanabe, Belson Rugwizangoga, Satoshi Baba, Hidetaka Yamada, Katsuhiro Yoshimura, Yasuhiro Sakai, Haruhiko Sugimura, Kazuya Shinmura
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Cancer, Vol 24, Iss 1, Pp 1-15 (2024)
Druh dokumentu: article
ISSN: 1471-2407
DOI: 10.1186/s12885-024-13009-8
Popis: Abstract Background Mutations in the TP53 tumor suppressor gene are well-established drivers of colorectal cancer (CRC) development. However, data on the prevalence of TP53 variants and their association with consensus molecular subtype (CMS) classification in patients with CRC from Rwanda are currently lacking. This study addressed this knowledge gap by investigating TP53 mutation status concerning CMS classification in a CRC cohort from Rwanda. Methods Formalin-fixed paraffin-embedded (FFPE) tissue blocks were obtained from 51 patients with CRC at the University Teaching Hospital of Kigali, Rwanda. Exons 4 to 11 and their flanking intron-exon boundaries in the TP53 gene were sequenced using Sanger sequencing to identify potential variants. The recently established immunohistochemistry-based classifier was employed to determine the CMS of each tumor. Results Sequencing analysis of cancerous tissue DNA revealed TP53 pathogenic variants in 23 of 51 (45.1%) patients from Rwanda. These variants were predominantly missense types (18/23, 78.3%). The most frequent were c.455dup (p.P153Afs*28), c.524G > A (p.R175H), and c.733G > A (p.G245S), each identified in three tumors. Trinucleotide sequence context analysis of the 23 mutations (20 of which were single-base substitutions) revealed a predominance of the [C > N] pattern among single-base substitutions (SBSs) (18/20; 90.0%), with C[C > T]G being the most frequent mutation (5/18, 27.8%). Furthermore, pyrimidine bases (C and T) were preferentially found at the 5ʹ flanking position of the mutated cytosine (13/18; 72.2%). Analysis of CMS subtypes revealed the following distribution: CMS1 (microsatellite instability-immune) (6/51, 11.8%), CMS2 (canonical) (28/51, 54.9%), CMS3 (metabolic) (9/51, 17.6%), and CMS4 (mesenchymal) (8/51, 15.7%). Interestingly, the majority of TP53 variants were in the CMS2 subgroup (14/23; 60.1%). Conclusion Our findings indicate a high frequency of TP53 variants in CRC patients from Rwanda. Importantly, these variants are enriched in the CMS2 subtype. This study, representing the second investigation into molecular alterations in patients with CRC from Rwanda and the first to explore TP53 mutations and CMS classification, provides valuable insights into the molecular landscape of CRC in this understudied population.
Databáze: Directory of Open Access Journals
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