Phosphatidylinositol 3-kinase (PI3KCA) Oncogene Mutation Analysis and Gene Expression Profiling in Primary Breast Cancer Patients

Kandula, Mahesh; Chennaboina, Kalyan Kumar; Ys, Ammi Raju; Raju, Suryanarayana

doi:10.7314/apjcp.2013.14.9.5067

Cited by 18 publications

(9 citation statements)

References 30 publications

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“…Our results support Kriegsmann et al experience, demonstrating that PIK3CA mutations are recognizable in a higher percentage (23.7%) of TNBC than previously reported in the literature [ 17 , 18 , 20 – 22 ]. Although histologic subtypes other than invasive ductal carcinoma are scarcely represented in our study, we could identify PIK3CA mutations in triple negative invasive lobular carcinoma, medullary carcinoma, and even in special variants of BC, as adenoid cystic carcinoma.…”

Section: Discussionsupporting

confidence: 93%

“…In this pathway, the most common genetic abnormality is represented by activating mutations in Phosphatidylinositol-4-5-bisphosphate-3-kinase catalytic subunit-α (PIK3CA) gene, with a reported frequency of 20–40% in BC [ 15 , 16 ]. PIK3CA mutations are more prevalent in ER/PgR positive (35%) and HER2-overexpressing BC (23%) than in TNBC (ranging from 5% to 13.2%) [ 17 – 22 ]. Recently, Kriegsmann et al demonstrated a high frequency of PI3K pathway alterations, comprising mainly PIK3CA mutations, in a large series of TNBC [ 23 ]; moreover, PIK3CA mutations were also identified in TNBC-homologous molecular subtype, i.e.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer

Cossu-Rocca

Orrù²,

Muroni

et al. 2015

PLoS ONE

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BackgroundTriple Negative Breast Cancer (TNBC) accounts for 12–24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20–40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.Materials and MethodsPIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.ResultsPIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.ConclusionsOur data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer

Cossu-Rocca

Orrù²,

Muroni

et al. 2015

PLoS ONE

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“…PI3K/Akt pathway is well known that it plays important role in cancer cell proliferation, catabolism, cell adhesion and apoptosis. And the PIK3CA amplification and mutations frequently has been found in various human cancers such as breast, cervical cancers, ovarian cancers, thyroid cancers, and pituitary tumors (Shayesteh et al, 1999;Ma et al, 2000;Samuels et al, 2004;Garcia-Rostan et al, 2005;Velho et al, 2005;Wu et al, 2005;Lin et al, 2009;Kandula et al 2013). In present study, however, we found relatively low frequency of PIK3CA mutations in the GC (7.7%).…”

Section: Discussioncontrasting

confidence: 69%

Are PIK3CA Mutation and Amplification Associated with Clinicopathological Characteristics of Gastric Cancer?

Lee

Hwang²,

Choi³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Alterations in mitochondrial DNA (mtDNA) have been studied in various cancers. However, the clinical value of mtDNA copy number (mtCN) alterations in gastric cancer (GC) is poorly understood. In the present study, we investigated whether alterations in mtCNs might be associated with clinicopathological parameters in GC cases. mtCN was measured in 109 patients with GC by real-time PCR. Then, correlations with clinicopathological characteristics were analyzed. mtCN was elevated in 64.2% of GC tissues compared with paired, adjacent, noncancerous tissue. However, the observed alterations in mtCN were not associated with any clinicopathological characteristics, including age, gender, TN stage, Lauren classification, lymph node metastasis, and depth of invasion. Moreover, Kaplan-Meier survival curves revealed that mtCN was not significantly associated with the survival of GC patients. In this study, we demonstrated that mtCN was not a significant marker for predicting clinical characteristics or prognosis in GC.

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“…PIP3, in turn, is required for translocation of AKT1, to the cell membrane, where it is phosphorylated and activated by upstream kinases [47]. PIK3CA activating mutations have been found in approximately 21-28% of primary stages I-IV BC patients [43,48,49]. PIK3CA mutations are mainly located in two hotspots of the helical domains (E542K and E545K, exon 9) and in the p110 catalytic subunit (H1047R, exon 20) [48,50].…”

Section: Pik3camentioning

confidence: 99%

De Novo Resistance Biomarkers to Anti-Her2 Therapies in Her2-Positive Breast Cancer

et al. 2015

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Therapies targeting HER2 receptor, overexpressed in 20% breast cancer (BC), improved prognosis, however ~62% patients experiment progression during the first year. Molecular mechanisms proposed to be responsible for this de novo resistance include HER2 modifications, defects in the antibody dependent cellular cytotoxicity or in cell arrest and apoptosis or alterations in HER2 signaling components. This article will review the influence of genetic markers investigated to date as cause of de novo resistance to HER2-targeted drugs in HER2-positive BC patients. Biomarkers like p95HER2, CCND1 and CDC25A have demonstrated clinical relevance and prognostic value in HER2-positive BC patients. However, the prognostic value of most biomarkers investigated to date, such as PIK3CA or AKT1, cannot be fully established yet.

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Phosphatidylinositol 3-kinase (PI3KCA) Oncogene Mutation Analysis and Gene Expression Profiling in Primary Breast Cancer Patients

Cited by 18 publications

References 30 publications

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer

Are PIK3CA Mutation and Amplification Associated with Clinicopathological Characteristics of Gastric Cancer?

De Novo Resistance Biomarkers to Anti-Her2 Therapies in Her2-Positive Breast Cancer

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