Mutation of the <i>PIK3CA</i> Gene in Anaplastic Thyroid Cancer

García-Rostán, Ginesa; Costa, Ângela M.; Pereira-Castro, Isabel; Salvatore, Giuliana; Hernández, Radhamés; Hermsem, Mario J.A.; Herrero, Agustín; Fusco, Alfredo; Cameselle-Teijeiro, José; Santoro, Massimo

doi:10.1158/0008-5472.can-04-4259

Cited by 315 publications

(218 citation statements)

References 25 publications

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“…11 The PI3K pathway is frequently activated in head and neck cancer through genomic amplification or activating mutation of the PIK3CA gene, or the loss of expression and/or function of the inhibitory Pten protein, that results in the activation of the Akt oncogenic signaling pathway. 11,[14][15][16][17] We have previously reported PIK3CA mutations in head and neck squamous cell carcinoma (HNSCC) (4/38, 11%), and 3 of the reported PIK3CA mutations were identified in 6 pharyngeal squamous cell carcinoma samples in the study. 11 Because of the small sample size in that study, the true mutation frequency of PIK3CA in pharyngeal cancer could not be determined.…”

mentioning

confidence: 67%

Novel mutant‐enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer

Qiu

Tong

Manolidis

et al. 2007

Intl Journal of Cancer

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We previously reported 4 PIK3CA mutations in 38 head and neck cancer samples, 3 of which were identified in 6 pharyngeal cancer samples. To determine the mutation frequency of PIK3CA in pharyngeal cancer, we studied 24 additional cases of pharyngeal squamous cell carcinoma in this study. Using both direct genomic DNA sequencing and novel mutant-enriched sequencing methods developed specifically for the 3 hot-spot mutations (H1047R, E545K and E452K) of PIK3CA, we detected 5 mutations of PIK3CA in the 24 pharyngeal cancers (20.8%). Three of the 5 mutations had been missed by the conventional sequencing method and were subsequently detected by novel mutant-enriched sequencing methods. We showed that the mutant-enriched sequencing method for the H1047R hot-spot mutation can identify the mutation in a mixed population of mutant and wild-type DNA sequences at 1:360 ratios. These novel mutant-enriched sequencing methods allow the detection of the PIK3CA hot-spot mutations in clinical specimens which often contain limited tumor tissues (i.e., biopsy specimens). The data further support that oncogenic PIK3CA may play a critical role in pharyngeal carcinogenesis, and the mutant-enriched sequencing methods for PIK3CA are sensitive and reliable ways to detect PIK3CA mutations in clinical samples. Because PIK3CA and its pathway are potential targets for chemotherapy and radiation therapy, and frequent somatic mutation of PIK3CA has been identified in many human cancer types (e.g., breast cancer, colorectal cancer), the abilities to detect PIK3CA mutations with enhanced sensitivities have great potential impacts on target therapies for many cancer types. ' 2007 Wiley-Liss, Inc.Key words: mutant-enriched sequencing method; PIK3CA oncogene; hot-spot mutation; pharyngeal cancer; HNSCC Oral and pharyngeal cancer accounts for over half a million new cancer cases and 2,710,000 deaths worldwide per annum. It is the sixth most common malignant tumors in the world. In the United States alone, there were 30,990 estimated new cancer cases and 7,430 new deaths in the oral cavity and pharynx in 2006. 1 Despite recent advances in surgical techniques and improvement in radiation therapy, the median survival of patients with head and neck cancer has changed little over the past few decades. 2 Thus, a better understanding of molecular and genetic feature of head and neck cancer would be critically helpful for the development of new methods for early diagnosis, monitoring and targeting therapy, and the eventual improvement in the survival rate. Recently, significant progress has been achieved in the understanding of the molecular genetic events underlying the development of oral squamous cell carcinoma, which includes inactivation of multiple tumor suppressor genes (p16, p53, p14 and FHIT) and activation of oncogenes (cyclin D1 and EGFR). 3,4 However, the molecular genetic profile of pharyngeal carcinogenesis is relatively less understood.PIK3CA, which is a member of PI3Ks family, has been demonstrated to function as an oncogene in some human ...

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confidence: 67%

Novel mutant‐enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer

Qiu

Tong

Manolidis

et al. 2007

Intl Journal of Cancer

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“…Akt-1 and Akt-2 were shown to be the most important genes in thyroid cancer [76]. It was previously determined that mutations, or amplification and genomic copy gain of the PI3KCA gene, encoding the catalytic subunit of PI3K, occur in thyroid tumors [77][78][79]. Decreased expression or inactivation of the tumor suppressor gene product PTEN and activation by RAS oncogenes have also been described to activate the PI3K/Akt signaling pathway and play a role in thyroid tumorigenesis [78][79][80].…”

Section: The Pi3k/akt Signaling Pathwaymentioning

confidence: 99%

An update on molecular biology of thyroid cancers

Ömür

Baran

2014

Critical Reviews in Oncology/Hematology

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“…Mutations were found in 10 of the 20 exons of this gene, with the helical (exon 9) and kinase (exon 20) domains harboring the most mutations. Since this initial discovery, PIK3CA mutations have been described in ovarian, hepatocellular, thyroid and endometrial cancers, acute leukemia, as well as in other central nervous system malignancies (3)(4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

PIK3CA Gene Mutations in Pediatric and Adult Glioblastoma Multiforme

Gallia¹,

Rand²,

Siu³

et al. 2006

Molecular Cancer Research

151

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The phosphatidylinositol 3-kinases (PI3K) are a family of enzymes that relay important cellular growth control signals. Recently, a large-scale mutational analysis of eight PI3K and eight PI3K-like genes revealed somatic mutations in PIK3CA, which encodes the p110A catalytic subunit of class IA PI3K, in several types of cancer, including glioblastoma multiforme. In that report, 4 of 15 (27%) glioblastomas contained potentially oncogenic PIK3CA mutations. Subsequent studies, however, showed a significantly lower mutation rate ranging from 0% to 7%. Given this disparity and to address the relation of patient age to mutation frequency, we examined 10 exons of PIK3CA in 73 glioblastoma samples by PCR amplification followed by direct DNA sequencing. Overall, PIK3CA mutations were found in 11 (15%) samples, including several novel mutations. PIK3CA mutations were distributed in all sample types, with 18%, 9%, and 13% of primary tumors, xenografts, and cell lines containing mutations, respectively. Of the primary tumors, PIK3CA mutations were identified in 21% and 17% of pediatric and adult samples, respectively. No evidence of PIK3CA gene amplification was detected by quantitative real-time PCR in any of the samples. This study confirms that PIK3CA mutations occur in a significant number of human glioblastomas, further indicating that therapeutic targeting of this pathway in glioblastomas is of value.Moreover, this is the first study showing PIK3CA mutations in pediatric glioblastomas, thus providing a molecular target in this important pediatric malignancy.

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Mutation of the PIK3CA Gene in Anaplastic Thyroid Cancer

Cited by 315 publications

References 25 publications

Novel mutant‐enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer

Novel mutant‐enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer

An update on molecular biology of thyroid cancers

PIK3CA Gene Mutations in Pediatric and Adult Glioblastoma Multiforme

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