Retracted: Frequent genetic and biochemical alterations of the PI 3‐K/AKT/PTEN pathway in head and neck squamous cell carcinoma

Pedrero, Juana Maria Garcia; Carracedo, Dario Garcia; Pinto, Cristina Muñoz; Zapatero, Agustín Herrero; Rodrigo, Juan P.; Nieto, Carlos Suárez; González, Marı́a Victoria

doi:10.1002/ijc.20711

Cited by 238 publications

(185 citation statements)

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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: 68%

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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mentioning

confidence: 68%

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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“…AKT1 amplification has been reported in various human cancers, including a single case of gliosarcoma (Knobbe and Reifenberger, 2003) and AKT3 mutation has been reported in a single case of glioma (Hunter et al, 2006); however, the consequence of this missense mutation (G171R) on the activity of the enzyme is unknown. While AKT2 amplification has been observed frequently in head and neck tumors, as well as pancreatic, ovarian and breast cancers (Bellacosa et al, 1995;Cheng et al, 1996;Pedrero et al, 2005;Nakayama et al, 2006), it has not yet been described in primary human brain tumors, although studies indicate it may be overexpressed and drive tumorigenicity in some glioma cell lines (Pu et al, 2006).…”

Section: Pi3k Pathway Involvement In Brain Tumorsmentioning

confidence: 99%

PTEN signaling in brain: neuropathology and tumorigenesis

2008

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“…Amplification of this region is associated with PrCa [72][73][74][75] and it contains the gene PIK3CA, which is associated with other tumors including breast, ovarian, colorectal and gastric cancers. [76][77][78][79][80] Some of these loci were found in subsets that already had some evidence of linkage to chromosome 2 or 17. These loci may not have been detected in the original linkage analyses because the effect on risk due to these loci is smaller than the effect on risk of the chromosome 2 or 17 loci, leading to insufficient power.…”

Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

et al. 2012

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Prostate cancer (PrCa) is the most common male cancer in developed countries and the second most common cause of cancer death after lung cancer. We recently reported a genome-wide linkage scan in 69 Finnish hereditary PrCa (HPC) families, which replicated the HPC9 locus on 17q21-q22 and identified a locus on 2q37. The aim of this study was to identify and to detect other loci linked to HPC. Here we used ordered subset analysis (OSA), conditioned on nonparametric linkage to these loci to detect other loci linked to HPC in subsets of families, but not the overall sample. We analyzed the families based on their evidence for linkage to chromosome 2, chromosome 17 and a maximum score using the strongest evidence of linkage from either of the two loci. Significant linkage to a 5-cM linkage interval with a peak OSA nonparametric allele-sharing LOD score of 4.876 on Xq26.3-q27 (DLOD ¼ 3.193, empirical P ¼ 0.009) was observed in a subset of 41 families weakly linked to 2q37, overlapping the HPCX1 locus. Two peaks that were novel to the analysis combining linkage evidence from both primary loci were identified; 18q12.1-q12.2 (OSA LOD ¼ 2.541, DLOD ¼ 1.651, P ¼ 0.03) and 22q11.1-q11.21 (OSA LOD ¼ 2.395, DLOD ¼ 2.36, P ¼ 0.006), which is close to HPC6. Using OSA allows us to find additional loci linked to HPC in subsets of families, and underlines the complex genetic heterogeneity of HPC even in highly aggregated families.

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Retracted: Frequent genetic and biochemical alterations of the PI 3‐K/AKT/PTEN pathway in head and neck squamous cell carcinoma

Cited by 238 publications

References 31 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

PTEN signaling in brain: neuropathology and tumorigenesis

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

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