Sporadic pediatric severe familial adenomatous polyposis: A case report

Cerasuolo, Andrea; Miele, Erasmo; Russo, Marina; Aversano, Antonietta; Cammarota, Francesca; Duraturo, Francesca; Liccardo, Raffaella; Izzo, Paola; Rosa, Marina De

doi:10.3892/mco.2020.2090

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…The mutation had occurred in a conserved amino acid position but it was predicted to be tolerated by SIFT and suggested to be benign by PolyPhen. In this respect, Picelli et al, 38 Cerasuolo et al, 39 and Fernández‑Rozadilla et al 40 concluded that it was not a disease causing variant because it was found equally distributed among normal and FAP‐affected individuals. Our analysis showed that only p. Arg653Met mutation is likely to have damaging and deleterious effects on the APC protein.…”

Section: Discussionmentioning

confidence: 99%

Mutational screening through comprehensive bioinformatics analysis to detect novel germline mutations in the APC gene in patients with familial adenomatous polyposis (FAP)

Ghadamyari

Heidari

Zeinali

et al. 2021

Clinical Laboratory Analysis

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Background Familial adenomatous polyposis (FAP) as a colon cancer predisposition syndrome is an autosomal‐dominant inherited condition and is diagnosed by the progress of hundreds or thousands of adenomatous colonic polyps in the colon. This study aims at the nature and effect of Adenomatous Polyposis Coli (APC) gene mutations in FAP tumorigenesis. Methods The genetic screening of 59 FAP Iranian patients in 10 families was performed by polymerase chain reactions and the direct sequencing of the entire coding exons of the APC gene. To do linkage haplotype analysis and multiplex PCR‐based microsatellite examination, six short tandem repeat loci were selected in this gene. To evaluate and predict the potentially deleterious effects, comprehensive bioinformatics pathogenicity assays were used. Results A total of 12 germline heterozygous and homozygous nucleotide variations were identified. They included two missense mutations, four nonsense mutations, which would lead to the truncated and nonfunctional protein products, four synonymous or silent variations, and two nucleotide deletions of 1 to 5 bp or frameshift mutations. In addition, three novel heterozygous nonsense mutations were found in exons 10, 14, and 15 of the gene. There was also p.Arg653Met as a novel heterozygote mutation in exon 14 of the gene. Conclusions Bioinformatics analysis and three‐dimensional structural modeling predicted that these missense and nonsense mutations generally are associated with the deleted or truncated domains of APC and have functional importance and mainly affected the APC protein. These findings may provide evidence for the progress of potential biomarkers and help to understand the role of the APC gene in FAP.

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Section: Discussionmentioning

confidence: 99%

Mutational screening through comprehensive bioinformatics analysis to detect novel germline mutations in the APC gene in patients with familial adenomatous polyposis (FAP)

Ghadamyari

Heidari

Zeinali

et al. 2021

Clinical Laboratory Analysis

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“…Many germline pathogenic variants in each of these genes cause the diseases' onset, with penetrance varying according to the specific syndrome [17][18][19][20]. We demonstrated that quantitative alterations in the expression of the same genes contribute to generate inter-and intra-familial phenotypic heterogeneity [21,22]. Furthermore, germline pathogenic variants in specific gene, such as the phosphatase and tensin 106 homolog (PTEN) gene, generate constitutive beta-catenin and cytokine dysregulation, activating inflammatory pathways and, in turn, increasing cancer risk of carrier subjects [23].…”

Section: Crcs: Epidemiology and Geneticsmentioning

confidence: 99%

The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation

et al. 2023

Self Cite

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Colorectal cancer (CRC) stands as the third most significant contributor to cancer-related mortality worldwide. A major underlying reason is that the detection of CRC usually occurs at an advanced metastatic stage, rendering therapies ineffective. In the progression from the in situ neoplasia stage to the advanced metastatic stage, a critical molecular mechanism involved is the epithelial-to-mesenchymal transition (EMT). This intricate transformation consists of a series of molecular changes, ultimately leading the epithelial cell to relinquish its features and acquire mesenchymal and stem-like cell characteristics. The EMT regulation involves several factors, such as transcription factors, cytokines, micro RNAs and long noncoding RNAs. Nevertheless, recent studies have illuminated an emerging link between metabolic alterations and EMT in various types of cancers, including colorectal cancers. In this review, we delved into the pivotal role played by EMT during CRC progression, with a focus on highlighting the relationship between the alterations of the tricarboxylic acid cycle, specifically those involving the succinate dehydrogenase enzyme, and the activation of the EMT program. In fact, emerging evidence supports the idea that elucidating the metabolic modifications that can either induce or inhibit tumor progression could be of immense significance for shaping new therapeutic approaches and preventative measures. We conclude that an extensive effort must be directed towards research for the standardization of drugs that specifically target proteins such as SDH and SUCNR1, but also TRAP1, PDH, ERK1/2, STAT3 and the HIF1-α catabolism.

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“…In humans, when germline variants likely associated with a certain disease are observed in patients, it is possible to examine their close relatives, such as parents and siblings, relatively easily to determine whether the disease is transmitted in association with the candidate DNA variant within the family. For example, while more than 3000 different germline APC variants causing FAP have been identified [ 17 ], novel pathogenic APC variants have still been discovered in recent studies in which examinations of family members were conventionally performed [ 18 , 19 , 20 , 21 ]. In contrast, it is challenging to trace the relatives of household dogs after disease onset.…”

Section: Introductionmentioning

confidence: 99%

First Evidence of Familial Transmission of Hereditary Gastrointestinal Polyposis Associated with Germline APC Variant in Jack Russell Terriers

Yoneji

Yoshizaki

Hirota

et al. 2023

Veterinary Sciences

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Jack Russell terriers (JRTs) with gastrointestinal (GI) neoplastic polyps have been recently reported to harbor an identical germline variant in the adenomatous polyposis coli (APC) gene, c.[462_463delinsTT], in the heterozygous state, which indicates that this disease is an autosomal dominant hereditary disorder. Many individual cases of this disease have been observed in clinical practice; however, familial transmission has not been demonstrated due to the difficulty in tracing the family members of household dogs, especially after the disease’s onset in adulthood. Recently, we encountered two cases of GI polyposis in maternal half sisters. These two cases facilitated the identification of additional relatives spanning three generations, including parents, full and half siblings of the dam (aunt and uncle), littermate and non-littermate siblings, and a nephew. Genetic analysis revealed that 11 of the 14 examined JRTs in this family carried the heterozygous germline APC variant, and eight dogs with the variant already had a current and/or past medical history of GI neoplastic polyps. Some cases in the family showed significantly more severe disease phenotypes than those initially reported, suggesting that the severity of this disease can vary considerably among individuals. Moreover, familial aggregation of severe cases suggested that the genetic modifier involved in increasing severity may have been transmitted in this family in addition to the germline APC variant. Furthermore, in addition to this family, we reported two other families of JRTs affected by hereditary GI polyposis that consisted of five full and half siblings and a mother–daughter pair, respectively. These findings unequivocally establish the transgenerational transmission of hereditary GI polyposis associated with the germline APC variant in JRT lineages.

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Sporadic pediatric severe familial adenomatous polyposis: A case report

Cited by 4 publications

References 24 publications

Mutational screening through comprehensive bioinformatics analysis to detect novel germline mutations in the APC gene in patients with familial adenomatous polyposis (FAP)

Mutational screening through comprehensive bioinformatics analysis to detect novel germline mutations in the APC gene in patients with familial adenomatous polyposis (FAP)

The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation

First Evidence of Familial Transmission of Hereditary Gastrointestinal Polyposis Associated with Germline APC Variant in Jack Russell Terriers

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