Five P53 SNPs Involved in Low Rectal Cancer Risk and Prognosis in a Chinese Population

Zhang, Guangzhe; Xu, Qian; Liu, Jingwei; Lv, Zhi; Lu, Youzhu; Yang, Huaiwei; Sun, Liping; Xing, Chengzhong; Yuan, Yuan

doi:10.7150/jca.26722

Cited by 4 publications

(2 citation statements)

References 31 publications

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“…Mutations and/or allelic variants in the TP53 gene have been proven to influence carcinogenesis, disease progression and/or response to treatment in several cancers including CRC [ 12 , 13 , 16 ]. The commonest TP53 mutations in different cancers are missense mutations, accounting for approximately 40%, followed by frameshift deletions in 20% and frameshift insertions in 10% [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

TP53 mutations in Romanian patients with colorectal cancer

Manirakiza,

Yamada,

Iwashita

et al. 2023

Genes and Environ

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Background Colorectal cancer (CRC) has been ranked as the second most deadly cancer and the third most diagnosed cancer cases for the year 2020. Specifically for Romania, the number of CRC-related deaths in 2019 was estimated at 6307 people, with a standardized mortality rate of 33.8 per 100,000 inhabitants. Although the tumor protein 53 (TP53) gene is intensively studied, there are few data on TP53 mutations in Romanian CRC. Furthermore, since genetic alterations may show geographical differences, our study aimed to analyze the clinical status and TP53 somatic variation in Romanian CRC patients. Subjects and methods DNA from 40 randomly selected cases of CRC was extracted from formalin-fixed paraffin-embedded tissues and sequenced using direct Sanger sequencing techniques, and variants were annotated according to the recommendations of the Human Genome Variation Society. Novel variants were analyzed using MutationTaster2021 to predict their effects. Results The mean age was 63.6 years (range 33–85 years) with a male to female ratio of 2.3. More than 45% (18/40) had an advanced cancer stage (≥ stage III). Mutations were found in 21/40 cases (52.5%), with one case having two mutations, giving a total of twenty-two mutations in the TP53 coding DNA. These mutations include 3 (13.6%) insertion-deletion mutations, two of which are novel frameshift mutations: c.165delT (in exon 4) and c.928_935dup (in exon 9), both of which are predicted to lead to nonsense-mediated mRNA decay and are classified as deleterious. The remaining 19 (86.36%) were substitution mutations: 1 nonsense and 18 (81.8%) missense mutations, with G > A (n = 7/19; 36.8%) and C > T (n = 6/19; 31.5%) transitions being the most common. The G > T transversion was found in 21.05% (4/19) of the substitution mutations. Conclusion We have described two novel frameshift mutations in TP53. The discovery of novel mutations following the efforts of The Cancer Genome Atlas and other large-scale cancer genome sequencing projects may be further evidence of the heterogeneous nature of mutations in cancer and may indicate that the identification of carcinogenic mutations is not yet saturated. Further sequencing is therefore needed, especially in less studied populations. Importantly, consideration of their geographical environment will shed light on population-specific carcinogenesis.

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Section: Introductionmentioning

confidence: 99%

TP53 mutations in Romanian patients with colorectal cancer

Manirakiza,

Yamada,

Iwashita

et al. 2023

Genes and Environ

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“…Improved from ASPCR, Kompetitive Allele Specific PCR (KASP, LGC Group) introduced fluorescence resonance energy transfer (FRET) for signal generation, where 2 fluorescent cassettes are used for identification of allele-specific amplification for a single bi-allelic SNP. Compared with other alternatives, KASP is more flexible [10], cost-effective [11] and robust [12], and therefore is now widely applied in large scale genotyping for many areas including agriculture [13] and human health [14,15]. However, due to KASP's closed platform, the multiplexity is limited to only single bi-allelic SNP in each reaction, restricting the further improvement of the throughput and efficiency.…”

Section: Introductionmentioning

confidence: 99%

Towards low cost, multiplex clinical genotyping: 4-fluorescent Kompetitive Allele-Specific PCR and its application on pharmacogenetics

Suo

Shi

et al. 2020

PLoS ONE

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Single-nucleotide polymorphisms (SNPs) is associated with efficacy of specific drugs. Although there are several methods for SNP genotyping in clinical settings, alternative methods with lower cost, higher throughout and less complexity are still needed. In this study, we modified Kompetitive Allele Specific PCR to enable multiplex SNP genotyping by introducing additional fluorescent cassettes that specifically help to differentiate more amplification signals in a single reaction. This new format of assay achieved a limit of detection down to 310 copies/ reactions for simultaneous detection of 2 SNPs with only standard endpoint PCR workflow for synthetic controls, and genotyped 117 clinical samples with results that were in 100% agreement with hospital reports. This study presented a simplified, costeffective high-throughput SNP genotyping alternative for pharmacogenetic variants, and enabled easier access to pharmaceutical guidance when needed.

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