A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix

Hara, Kieko; Saito, Tsuyoshi; Hayashi, Takuo; Yimit, Alkam; Takahashi, Michiko; Mitani, Keiko; Takahashi, Makoto; Yao, Takashi

doi:10.1016/j.prp.2015.06.004

Cited by 44 publications

(26 citation statements)

References 32 publications

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“…They rarely show high levels of microsatellite instability. [47][48][49] In our experience, precursor lesions associated with mucinous adenocarcinomas are often serrated polyps, LAMNs or HAMNs. Non-mucinous adenocarcinomas are more likely to be associated with an adenoma resembling the usual colorectal type, although exceptions occur.…”

Section: Adenocarcinoma Of the Appendixmentioning

confidence: 93%

The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei

Carr¹,

et al. 2017

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The vermiform appendix is the primary site of several distinctive benign and malignant neoplasms. Some can produce the clinical syndrome of pseudomyxoma peritonei (PMP). A consensus on their terminology was reached by an international panel of pathologists and clinicians working under the auspices of the Peritoneal Surface Oncology Group International (PSOGI), and this review discusses the application of the PSOGI classification to routine reporting. We discuss diagnosis and differential diagnosis together with implications for patient management, covering low-grade appendiceal mucinous neoplasms, high-grade appendiceal mucinous neoplasms, serrated polyps, adenomas and adenocarcinomas. We do not cover goblet cell tumours or neuroendocrine neoplasms in this paper.

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Section: Adenocarcinoma Of the Appendixmentioning

confidence: 93%

The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei

Carr¹,

et al. 2017

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“…The molecular pathogenesis of appendiceal epithelial neoplasms remains to be clarified. LAMNs with or without PMP have been found to frequently harbour activating mutations in KRAS and GNAS . TP53 and APC mutations have also been reported, but the mutation frequencies were quite variable among studies .…”

Section: Introductionmentioning

confidence: 99%

“…LAMNs with or without PMP have been found to frequently harbour activating mutations in KRAS and GNAS. [4][5][6][7][8][9][10][11] TP53 and APC mutations have also been reported, but the mutation frequencies were quite variable among studies. 6,7,10 Pai et al reported a high frequency of KRAS mutation and a much lower frequency of BRAF mutation in serrated lesions.…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7][8][9][10][11] TP53 and APC mutations have also been reported, but the mutation frequencies were quite variable among studies. 6,7,10 Pai et al reported a high frequency of KRAS mutation and a much lower frequency of BRAF mutation in serrated lesions. 16 Although most genetic studies have been conducted after the PSOGI meeting that established uniform terminology and definitions, the terminology has not been adopted by all studies and the morphology of the tumours analysed has not been described in detail.…”

Section: Introductionmentioning

confidence: 99%

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Correlation of molecular and morphological features of appendiceal epithelial neoplasms

et al. 2019

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Aims The aims of this study were to identify the genetic features of appendiceal epithelial neoplasms and correlate the genetic features with morphology. Methods and results We analysed the genetic features of a series of 47 appendiceal epithelial neoplasms of various morphologies by using targeted next‐generation sequencing of 11 genes commonly mutated in gastrointestinal neoplasms. Seven of nine serrated polyps harboured BRAF mutations, which are rare in other types of appendiceal tumours. Most cases of low‐grade appendiceal mucinous neoplasms (LAMNs) exhibited GNAS and KRAS mutations. LAMNs with a coexisting serrated polyp were all KRAS mutated. Four LAMNs with mutations in the Wnt/β‐catenin pathway, either through inactivating mutations in APC or RNF43 or activating mutations in CTNNB1, had focal proliferation of mucin‐poor low‐grade tumour cells, reminiscent of colorectal adenomas. Mutations in the Wnt/β‐catenin pathway were also identified in high‐grade appendiceal mucinous neoplasms, suggesting that Wnt/β‐catenin pathway activation is the driving force for the progression of LAMN to a higher‐grade lesion. Adenomatous polyps of the appendix frequently had APC, KRAS and TP53 mutations and were morphologically and molecularly similar to adenomatous polyps of the colorectum. Conclusions Our results indicate a close association between morphology and genetic events in appendiceal neoplasms and suggest a phylogenetic relationship between different entities.

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“…It has been shown that KRAS is frequently mutated in the majority of low-grade appendiceal neoplasms and mucinous adenocarcinomas, whereas GNAS mutation is only observed in of low-grade appendiceal neoplasms. [10] Overexpression of p53 is reported to be rare in appendiceal tumours and, although KRAS mutation and p53 overexpression can be seen in half of PMP cases of appendiceal origin. [11] Microsatellite instability has also been shown to be rare in appendiceal carcinoma, and hyper-methylation is not a mechanism for genetic instability in these tumours although some hyperplastic polyps and sessile serrated adenomas of the appendix show decreased expression of MLH1 and BRAF mutation is more common in serrated polyps.…”

Section: Discussionmentioning

confidence: 99%

Familial appendiceal tumours in Diffuse Peritoneal Adenomucinosis and peritoneal mucinous carcinomatosis: A rare familial predisposition?

Davies

Doyle

Tran

et al. 2016

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Epithelial neoplasms of the appendix are rare. They account for an annual age adjusted incidence of 4 cases per 1,000,000. The low incidence of primary appendix tumours means that there are very few published reports of the familial occurrence. This case series reports two cases of primary appendiceal epithelial tumours in two sets of relatives. A genetic evaluation was performed to determine if there was any underlying single gene disorder, which could account for the familial occurrence. The results showed there was no DNA mismatch repair defect evident. This means that the occurrence of appendiceal cancer in siblings may represent a random event. However, exceedingly rare predisposition syndrome cannot be ruled out from our analysis.

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A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix

Cited by 44 publications

References 32 publications

The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei

The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei

Correlation of molecular and morphological features of appendiceal epithelial neoplasms

Familial appendiceal tumours in Diffuse Peritoneal Adenomucinosis and peritoneal mucinous carcinomatosis: A rare familial predisposition?

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