Analysis of PIK3CA and Akt/protein kinase B in head and neck squamous cell carcinoma

Fenic, Irina; Steger, Klaus; Gruber, C.; Arens, Christoph; Woenckhaus, J. W.

doi:10.3892/or.18.1.253

Cited by 48 publications

(51 citation statements)

References 27 publications

(49 reference statements)

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“…PIK3CA alterations have been associated with cancer recurrence [26]; metastasis [12,13] and poor prognosis [27,28] in a variety of human cancers. In HNSCC, PIK3CA alterations correlate with advanced stage [29,30], vascular invasion [31], and lymph node metastasis [32]. In our study we found a higher mutational frequency of PIK3CA (E545A-46.51% and T1025T-41.08%) in HNSCC.…”

Section: Discussionsupporting

confidence: 63%

Association of PIK3CA gene mutations with head and neck squamous cell carcinomas

Kommineni¹,

Jamil²,

Pingali³

et al. 2015

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The Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) is an important regulator of cell signaling pathways in human cancers. Mutations in PIK3CA were found to be associated with more aggressive clinical outcome and aberrant activation of cellular mechanisms in cancers. Hence the present study aimed to understand the mutations in the PIK3CA gene in head and neck squamous cell carcinomas (HNSCC). After the approval of the Institutional Ethics Committee we recruited 129 HNSCC patients and 150 healthy controls for screening of mutations in the helical (exon9) and kinase domain (exon 20) of the PIK3CA gene using PCR, SSCP and Sanger Sequencing. We found about 60.46% of HNSCC patients and 26% of controls with the following mutations 1634A>C (E545A) and 3075C>T (T1025T) in the helical and kinase domains of PIK3CA. Both these mutations 1634A>C and 3075C>T were more prominent in oral cancers, advanced stages of HNSCC and tobacco plus alcohol habits (p<0.05). Hence, we conclude that the distribution of mutations of PIK3CA in HNSCC were associated with demographic (tobacco and alcohol) and clinical parameters (advanced stage, primary site) of HNSCC. It is possible that when this pathway is overactive due to mutations, it may reduce apoptosis and allow proliferation of the tumor cells. Therefore we propose that these mutations may serve as prognostic biomarkers, and can also be proposed as novel therapeutic targets for HNSCC.

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Section: Discussionsupporting

confidence: 63%

Association of PIK3CA gene mutations with head and neck squamous cell carcinomas

Kommineni¹,

Jamil²,

Pingali³

et al. 2015

neo

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“…Consequently, a strong association between the expression of PIK3CA and phospho-AKT was identified (P = 0.005, Fischer's exact test), and has been observed in other tumor types, e.g. squamous cell carcinoma of the head and neck and ovarian carcinoma [23,24]. In contrast to protein expression level, PIK3CA mutations did not correlate with increased phospo-AKT expression, which may be explained by transcriptional or posttranscriptional mechanisms that determine the expression level of the catalytic subunit of PIK3CA.…”

Section: Discussionmentioning

confidence: 91%

Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer

et al. 2009

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The phosphatidylinositol 3-kinases-AKT-mammalian target of rapamycin pathway (PI3K/AKT/mTOR) is central in colorectal tumors. Data on its role in hereditary cancers are, however, scarce and we therefore characterized mutations in PIK3CA and KRAS, and expression of PIK3CA, phosphorylated AKT, and PTEN in colorectal cancers linked to hereditary nonpolyposis colorectal cancer (HNPCC). Sequencing was used to identify mutations in PIK3CA, a real-time PCR-based method to identify KRAS mutations, and immunohistochemical staining was used to evaluate the expression of PIK3CA, phosphorylated AKT and PTEN in 58 HNPCC-associated colorectal cancers. Derangements of at least one of the PI3K/AKT/mTOR components analyzed were found in 51/58 (88%) tumors. Mutations in PIK3CA and KRAS were identified in 14 and 31% of the tumors respectively. Overexpression of PIK3CA and phosphorylated AKT occurred in 59 and 75% and were strongly associated (P = 0.005). Reduced/lost PTEN expression was found in 63% of the tumors. Though HNPCC-associated colorectal cancers show simple genetic profiles with few chromosomal alterations, we demonstrate frequent and repeated targeting of the PI3K/AKT/mTOR pathway, which suggests that therapeutic strategies directed at this pathway are likely to be beneficial also in HNPCC.

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“…Mutations in PIK3CA and RAS genes have been found to be mutually exclusive in some cancers. However, PIK3CA and RAS mutations coexisted in familial colorectal carcinoma (Velho et al 2005), endometrial carcinoma (Fenic et al 2007), head and neck squamous cell carcinoma (Murugan et al 2008), and anaplastic thyroid cancer (Santarpia et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors

Lin¹,

Jiang²,

Ye³

et al. 2009

Endocrine-Related Cancer

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Genetic alterations in the PIK3CA gene of the phosphoinositide 3-kinase (PI3K)/AKT pathway have been found in many human tumors, but they have not been explored in pituitary tumors. We undertook the present study to explore mutations and amplifications of the PIK3CA gene in pituitary tumors. DNA sequencing and real-time quantitative PCR were used to examine mutations and amplifications respectively, on genomic DNA samples isolated from 353 cases of pituitary tumors, and immunohistostaining was used to assess PIK3CA expression. About 8 out of 91 (9%) invasive pituitary tumors versus 0 out of 262 (0%) noninvasive tumors were found to harbor somatic mutations in exons 9 and 20 of the PIK3CA gene (P!0.001), and the mutation was associated with increased disease recurrence. Genomic PIK3CA amplifications (defined as R4 copies) were observed in both invasive and noninvasive tumors, with a prevalence of around 20-40% in various types of pituitary tumors. PIK3CA protein overexpression was observed in cases with high PIK3CA copy number. RAS mutations were also examined and found in 6 out of the 91 (7%) invasive tumors. PIK3CA amplifications were mutually exclusive with PIK3CA or RAS mutations (P!0.001). This study demonstrated for the first time relatively common PIK3CA mutations and amplifications as well as RAS mutations and their tendency of mutual exclusivity in pituitary tumors. The data provide strong genetic evidence supporting a role of the PI3K/AKT signaling pathway in the tumorigenesis of pituitary tumors, particularly the invasive types.

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Analysis of PIK3CA and Akt/protein kinase B in head and neck squamous cell carcinoma

Cited by 48 publications

References 27 publications

Association of PIK3CA gene mutations with head and neck squamous cell carcinomas

Association of PIK3CA gene mutations with head and neck squamous cell carcinomas

Frequent alterations of the PI3K/AKT/mTOR pathways in hereditary nonpolyposis colorectal cancer

Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors

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