Somatic Mutation of the <i>APC</i> Gene in Thyroid Carcinoma Associated with Familial Adenomatous Polyposis

Iwama, Takeo; Konishi, Motoko; Iijima, Takeru; Yoshinaga, Keigo; Tominaga, Takeshi; Koike, Masato; Miyaki, Michiko

doi:10.1111/j.1349-7006.1999.tb00757.x

Cited by 25 publications

(19 citation statements)

References 27 publications

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“…The molecular link between FAP and the cribiform morular variant of PTC is the APC gene, since germline and/or somatic alterations have been detected in FAP-associated, as well as in sporadic thyroid carcinomas with a cribiform-morular appearance (95,96). Moreover, the APC deleterious mutations related to these tumours are associated with the 5' region of exon 15 and are unfrequent in the considered hotspot mutation region of APC (97).…”

Section: Molecular Genetics Of Papillary Thyroid Carcinomamentioning

confidence: 99%

Molecular genetics of papillary thyroid carcinoma: great expectations...

Trovisco

Soares

Preto

et al. 2007

Arq Bras Endocrinol Metab

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Papillary thyroid carcinoma (PTC) is the most prevalent type of endocrine cancer and, in recent epidemiological surveys, one of the types of human cancer whose incidence is growing. Despite the favourable outcome and long survival rates of most patients, some tumours display an aggressive behaviour and may progress to the highly aggressive and lethal, anaplastic thyroid carcinoma. In recent years, several progresses have been made on the molecular characterization of PTC, in general, and in the genetic alterations underlying the histotype diversity of this type of cancer, in particular. This holds true regarding alterations on nuclear DNA as well as mitochondrial DNA. In this review we have summarized the most recent findings in the genetic characterization of PTC, giving a particular emphasis to the genotype-phenotype associations, the prognosis implications, and the diagnostic and therapeutic value of the newly identified genetic markers. RESUMOGenética Molecular do Carcinoma Papilífero de Tireóide -Grandes Esperanças… O carcinoma papilífero de tireóide (CPT) é o tipo mais prevalente de câncer endócrino e, em pesquisas epidemiológicas recentes, um dos tipos de câncer humano cuja incidência vêm crescendo. A despeito do prognóstico favorável e da longa taxa de sobrevivência da maioria dos pacientes, alguns tumores mostram um comportamento agressivo e podem progredir para o altamente agressivo e letal carcinoma anaplásico de tireóide. Recentemente, vários progressos foram feitos quanto à caracterização molecular do CPT, em general, e às alterações genéticas subjacentes à diversidade histológica desse tipo de câncer, em particular, particularmente com respeito às alterações dos DNAs nuclear e mitocondrial. Nesta revisão, nós sumarizamos os achados mais recentes da caracterização genética do CPT, dando ênfase particular às associações genótipo-fenótipo, às implicações prognósticas e ao valor diagnóstico e terapêutico dos marcadores genéticos recentemente identificados.

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Section: Molecular Genetics Of Papillary Thyroid Carcinomamentioning

confidence: 99%

Molecular genetics of papillary thyroid carcinoma: great expectations...

Trovisco

Soares

Preto

et al. 2007

Arq Bras Endocrinol Metab

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“…In the literature, 18 of 28 (64%) of CMV-PTC tested positive for aberrations in APC gene. Both somatic and germline mutations of APC were reported in CMV-PTC (Iwama et al 1999, Uchino et al 2006.…”

Section: Wnt Signalling Pathwaymentioning

confidence: 99%

Cribriform-morular variant of papillary thyroid carcinoma: a distinctive type of thyroid cancer

Lam¹,

Saremi²

2017

Endocrine-Related Cancer

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The aim of this systematic review is to study the features of cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) by analysing the 129 documented cases in the English literature. The disease occurred almost exclusively in women. The median age of presentation for CMV-PTC was 24 years. Slightly over half of the patients with CMV-PTC had familial adenomatous polyposis (FAP). CMV-PTC presented before the colonic manifestations in approximately half of the patients with FAP. Patients with FAP often have multifocal tumours in the thyroid. Microscopic examination of CMV-PTC revealed predominately cribriform and morular pattern of cancer cells with characteristic nuclear features of papillary thyroid carcinoma. Psammoma body is rare. On immunohistochemical studies, β-catenin is diffusely positive in CMV-PTC. The morular cells in CMV-PTC are strongly positive for CD10, bcl-2 and E-cadherin. Pre-operative diagnosis of CMV-PTC by fine-needle aspiration biopsy could be aided by cribriform architecture, epithelial morules and β-catenin immunostaining. Mutations of APC gene are found in the patients with CMV-PTC associated with FAP. In addition, mutations in CTNNB1, RET/PTC rearrangement and PI3K3CA mutations have been reported. BRAF mutation is negative in all CMV-PTC tested. Compared to conventional papillary thyroid carcinoma, CMV-PTC had a lower frequency of lymph node metastases at presentation (12%) and distant metastases (3%) as well as lower recurrence rates (8.5%) and patients' mortality rates (2%). To conclude, patients with CMV-PTC have distinctive clinical, pathological and molecular profiles when compared to conventional papillary thyroid carcinoma.

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“…The clinical course of this 26-year-old woman has also been reported previously. 7) Germline APC mutation was detected at codon 175 (ACT to AT, C deletion), resulting in truncation at codon 184. A somatic mutation was also demonstrated at codon 886 (CAG to TAG, stop) in one of the thyroid carcinomas.…”

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confidence: 99%

Nuclear Localization of Immunoreactive β‐Catenin Is Specific to Familial Adenomatous Polyposis in Papillary Thyroid Carcinoma

Kurihara

Shimizu

Chong

et al. 2000

Japanese Journal of Cancer Research

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Thyroid carcinoma is the first symptom in some patients with familial adenomatous polyposis (FAP). We evaluated the cellular localization of β β β β-catenin in thyroid carcinomas associated (n = = = =4)or not associated (n = Thyroid carcinoma occurs much more frequently in young female patients with familial adenomatous polyposis (FAP) than in matched controls.=1, 2) The relative risk for thyroid carcinoma in FAP women under 35 years of age is 160 times normal, and more importantly, 30% of thyroid carcinomas are diagnosed 4-12 years before the development of polyposis.2) Germline mutation of the adenomatous polyposis coli gene (APC) is responsible for the FAP. APC protein controls the nuclear accumulation of β-catenin, a transcriptional activator regulated by the Wnt signaling pathway, by a combination of nuclear export and cytoplasmic degradation.3, 4) The latter function of APC is lost by the mutation and/or deletion of APC in both alleles in the colon carcinomas of FAP patients, and this results in the nuclear accumulation of β-catenin.5) Then, it interacts with Tcf-4, the Lef/TCf transcription factor, leading to activation of several developmentally related genes, such as c-myc, and subsequent cell proliferation. To test the possibility that the abnormality of the APC/β-catenin pathway is also involved in FAP-associated thyroid carcinoma, we immunohistochemically evaluated β-catenin in FAP-associated thyroid carcinoma as well as sporadic thyroid carcinomas. If β-catenin-accumulation is specific to FAP in thyroid carcinomas, it can be a hallmark to identify occult FAP in young patients with thyroid carcinoma.Four FAP patients with thyroid carcinoma were enrolled in this study. Three were sisters and the other was a daughter of one of them. The thyroid carcinoma was the first symptom of the proband at age 16, five years before the diagnosis of FAP with a rectal carcinoma. Thyroid carcinomas were detected at the age of 12 in the case of her sister, and at 13 in her daughter. The clinical course of the sisters has been previously reported, and germline APC mutation was found at codon 848 (AAA to TAA, stop). 6) In the case of the fourth patient, who had no relation to the three patients described above, multiple colon carcinomas and multiple thyroid carcinomas were diagnosed simultaneously (Fig. 1A). The clinical course of this 26-year-old woman has also been reported previously.7) Germline APC mutation was detected at codon 175 (ACT to AT, C deletion), resulting in truncation at codon 184. A somatic mutation was also demonstrated at codon 886 (CAG to TAG, stop) in one of the thyroid carcinomas.As for the sporadic thyroid carcinomas, two series were evaluated: the first series was papillary thyroid carcinomas which had been consecutively resected at the Department of Surgery, Jichi Medical School (n=140, age 17-83 years old), including 11 cases younger than 30 years of age. The second series consisted of thyroid carcinomas of patients aged less than 30, treated at Tokyo Metropolitan Komagome Hospital. Twenty-seve...

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Somatic Mutation of the APC Gene in Thyroid Carcinoma Associated with Familial Adenomatous Polyposis

Cited by 25 publications

References 27 publications

Molecular genetics of papillary thyroid carcinoma: great expectations...

Molecular genetics of papillary thyroid carcinoma: great expectations...

Cribriform-morular variant of papillary thyroid carcinoma: a distinctive type of thyroid cancer

Nuclear Localization of Immunoreactive β‐Catenin Is Specific to Familial Adenomatous Polyposis in Papillary Thyroid Carcinoma

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