Detection of APC mosaicism by next-generation sequencing in an FAP patient

Yamaguchi, Kiyoshi; Komura, Mitsuhiro; Yamaguchi, Rui; Imoto, Seiya; Shimizu, Eigo; Kasuya, Shinichi; Shibuya, Tetsuo; Hatakeyama, Seira; Takahashi, Norihiko; Ikenoue, Tsuneo; Hata, Katsuya; Tsurita, Giichiro; Shinozaki, Masaru; Suzuki, Yutaka; Sugano, Sumio; Miyano, Satoru; Furukawa, Yoichi

doi:10.1038/jhg.2015.14

Cited by 33 publications

(28 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…31,32 In the three patients tested by NGS in the present series, a previously PTT undetected exon 15 mutation was found in one patient, which is in accordance with these data.…”

Section: Discussionsupporting

confidence: 80%

Sporadic colorectal cancer: Studying ways to an end

Rosa

Fidalgo

Filipe³

et al. 2016

UEG Journal

View full text Add to dashboard Cite

Introduction: Although colorectal cancer (CRC) has often been regarded as a single entity, different pathways may lead to macroscopically similar cancers. These pathways may evolve into a patchy colonic field defect that we aimed to study in consecutive CRC patients. Methods: In a single-center, observational, prospective study, consecutive CRC patients were included if surgery and a perioperative colonoscopy were planned. Personal and familial history data were collected. Tumors were studied for microsatellite instability (MSI) status, DNA repair protein expression (DRPE) and presence of BRAF and/or APC mutations.Macroscopically normal mucosa samples were tested for APC mutations. Presence and location of synchronous and metachronous adenomas and patient follow-up were analyzed. The association of two categorical variables was tested through the Fisher's exact test (SPSS 19). Results: Twenty-four patients (12 male, mean age 69 years) were studied. High-grade MSI (MSI-H) was found in eight tumors-these were significantly more common in the right colon (p ¼ 0.047) and more likely to have an altered DRPE (p ¼ 0.007). BRAF mutation was found in two of six tested MSI-H tumors. APC gene mutations were found in nine of 16 non-MSI-H tumors and absent in normal mucosa samples. There was a nonsignificant co-localization of CRC and synchronous adenomas and a significant co-localization (p ¼ 0.05) of synchronous and metachronous adenomas. Discussion: Sporadic CRCs evolve through distinct pathways, evidenced only by pathological and molecular analysis, but clinically relevant both for patients and their families. In non-MSI-H tumors, the expected APC gene mutations were not detected by the most commonly used techniques in a high number of cases. More studies are needed to fully characterize these tumors and to search for common early events in normal mucosa patches, which might explain the indirect evidence found here for a field defect in the colon.

show abstract

“…31,32 In the three patients tested by NGS in the present series, a previously PTT undetected exon 15 mutation was found in one patient, which is in accordance with these data.…”

Section: Discussionsupporting

confidence: 80%

Sporadic colorectal cancer: Studying ways to an end

Rosa

Fidalgo

Filipe³

et al. 2016

UEG Journal

View full text Add to dashboard Cite

show abstract

“…Similarly, mutations in these patients cannot be detected by fluorescent in situ hybridization (FISH), which is used to detect large chromosomal arrangements in APC , suggesting that the known mechanisms leading to FAP are limited [25–28]. Recently, several groups facilitated next-generation sequencing to identify comprehensive causative variants of APC such as exon inversion and somatic mosaicism [26–28]. As a powerful high-throughput tool, next-generation sequencing might replace existing screening strategies for polyposis in the future because of its convenience and dramatically decreasing cost [1, 25, 26].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, several groups facilitated next-generation sequencing to identify comprehensive causative variants of APC such as exon inversion and somatic mosaicism [26–28]. As a powerful high-throughput tool, next-generation sequencing might replace existing screening strategies for polyposis in the future because of its convenience and dramatically decreasing cost [1, 25, 26]. …”

Section: Discussionmentioning

confidence: 99%

Three novel mutations of APC gene in Chinese patients with familial adenomatous polyposis

Liu

et al. 2016

Tumor Biol.

View full text Add to dashboard Cite

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized by the development of hundreds to thousands of colonic adenomas and an increased risk of colorectal cancer. Adenomatous polyposis coli (APC), encoding a large multidomain protein involved in antagonizing the Wnt signaling pathway, has been identified as the main causative gene responsible for FAP. In this study, we identified three novel mutations as well as two recurrent mutations in the APC in five Chinese FAP families by sequencing. Immunohistochemical analysis revealed that among these mutations, a nonsense mutation (c.2510C>G) and two small deletions (c.2016_2047del, c.3180_3184del) led to the truncation of the APC protein and the cytoplasmic and nuclear accumulation of β-catenin in the colorectal samples from affected individuals, respectively. Our study expands the database on mutations of APC and provides evidence to understand the function of APC in FAP.

show abstract

“…For example, because of its implications for other endocrine systems, it is important to confirm a diagnostic suspicion of Albright hereditary osteodystrophy by testing for mutations in GNAS gene [7]. Because this disorder is due to post-zygotic somatic mutations, the ability of NGS sequencing to detect mosaicism (which is not detected by traditional Sanger sequencing) improves the sensitivity of molecular testing at this locus [8]. Knowing that the mutation is present will prompt the health care provider to test for other associated endocrinopathies, resulting from resistance to TSH, gonadotropins, GHRH, or antidiuretic hormone.…”

Section: Approach To Disease Process and Clinical Implications Of Genmentioning

confidence: 99%

Next generation sequencing in endocrine practice

Forlenza

Calhoun

Beckman

et al. 2015

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

With the completion of the Human Genome Project and advances in genomic sequencing technologies, the use of clinical molecular diagnostics has grown tremendously over the last decade. Next-generation sequencing (NGS) has overcome many of the practical roadblocks that had slowed the adoption of molecular testing for routine clinical diagnosis. In endocrinology, targeted NGS now complements biochemical testing and imaging studies. The goal of this review is to provide clinicians with a guide to the application of NGS to genetic testing for endocrine conditions, by compiling a list of established gene mutations detectable by NGS, and highlighting key phenotypic features of these disorders. As we outline in this review, the clinical utility of NGS-based molecular testing for endocrine disorders is very high. Identifying an exact genetic etiology improves understanding of the disease, provides clear explanation to families about the cause, and guides decisions about screening, prevention and/or treatment.

show abstract

Detection of APC mosaicism by next-generation sequencing in an FAP patient

Cited by 33 publications

References 21 publications

Sporadic colorectal cancer: Studying ways to an end

Sporadic colorectal cancer: Studying ways to an end

Three novel mutations of APC gene in Chinese patients with familial adenomatous polyposis

Next generation sequencing in endocrine practice

Contact Info

Product

Resources

About