Patterns of <i>PIK3CA</i> alterations in familial colorectal and endometrial carcinoma

Ollikainen, Miina; Gylling, Annette; Puputti, Marjut; Nupponen, Nina N.; Abdel‐Rahman, Wael M.; Bützow, Ralf; Peltomäki, Païvi

doi:10.1002/ijc.22768

Cited by 61 publications

(45 citation statements)

References 35 publications

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“…Though previous studies have investigated the role of PI3K mutation and MSI in CRC, the data are in part conflicting. While Samuels et al (2004) found a significantly higher frequency of PIK3CA mutation in MMR deficient tumors compared to MMR proficient tumors (16/33 vs 58/201, P ¼ 0.014), others failed to highlight this correlation (Velho et al, 2005;Ollikainen et al, 2007). Our study showed significantly higher PIK3CA mutations within the MSI subset of CRC (35.9%).…”

Section: Discussioncontrasting

confidence: 57%

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Abubaker¹,

Bavi²,

Al-harbi³

et al. 2008

Oncogene

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Activation of the phosphatidylinositol 3 0 -kinase (PI3K)/ AKT pathway results in an increase in cell proliferation and survival. Somatic mutations within the PI3K catalytic subunit, PIK3CA are common cause of increasing PI3K activity and are believed to be oncogenic in many cancer types. Few reports addressed the association between PIK3CA mutations and tumor progression specifically in microsatellite instable (MSI) colorectal cancer (CRC). In the present study, we have evaluated PIK3CA mutational status in a series of 410 Middle Eastern CRC and 13 colon cell lines to study the prevalence of PIK3CA mutations in MSI cases, PTEN expression in CRC and possibility of therapeutic targeting of this set of patients. PIK3CA mutations were found in four of the cell lines tested and 51 colorectal carcinomas (12.2%). Three of these four mutated cell lines were MSI. PTEN was inactivated in 66.1% of the CRC. Furthermore, we observed a strong association between PIK3CA mutations and MSI status (P ¼ 0.0046) while PTEN loss was more frequent in microsatellite stable (MSS) CRC (P ¼ 0.043). A high prevalence of genetic alterations in PI3K/AKT pathway in Saudi cohort of CRC, predominance of PIK3CA mutations in the MSI subgroup and their possible involvement in development/progression of this subset of CRC are some of the significant findings of our study.

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Section: Discussioncontrasting

confidence: 57%

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Abubaker¹,

Bavi²,

Al-harbi³

et al. 2008

Oncogene

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“…This finding supports the basic evidence that AKT activation accompanied by PTEN inactivation is a key step in the development and/or progression of endometrial carcinomas. PIK3CA that encodes the catalytic subunit p110 of PI3K is also found to be frequently mutated in endometrial carcinoma and support the hypothesis that PIK3CA mutations may have an additive effect to PTEN monoallelic inactivation in endometrial carcinoma (Velasco et al 2006, Ollikainen et al 2007). Since, PIK3CA mutations were reported to be more common in tumors with PTEN mutations compared with those without PTEN mutations (Oda et al 2005).…”

Section: Cell Survival Pathwayssupporting

confidence: 64%

Resistance to chemotherapy and hormone therapy in endometrial cancer

Chaudhry¹,

Asselin²

2009

Endocrine-Related Cancer

113

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Endometrial cancer is the most common gynecological malignancy in developed countries and represents the eighth leading cause of cancer related death in women. The growing incidence of endometrial cancer leads scientists and oncologists to identify effective preventive measures and also molecular markers for diagnosis and prognosis. Chemotherapy and hormone therapy is the mainstay treatment option for advanced and recurrent endometrial cancer and response to therapy is one of the most important factor which favors prognosis and overall survival. In recent years, there have been major advances in the treatment of patients with endometrial cancer. Despite advances made in the treatment of this cancer, the overall survival of patients has not significantly improved because considerable number of patients harbor tumor refractory to these therapies and the majority of the initially responsive tumors become refractory to treatments. Therefore, determination of sensitivity/resistance is becoming increasingly important for individualization of endometrial cancer therapy. The aim of this review is to present the existing knowledge about the molecular markers that could play a crucial role in determining resistance to chemo-and hormone therapy. Extensive literature search for the cell signaling pathways and factors responsible for chemoresistance have been performed and reviewed. Several recent studies suggest that deregulations in the apoptotic pathways (such as p53, Fas/FasL, Bcl-2 family proteins, inhibitor of apoptosis proteins), survival pathways (PI3K/AKT, MAPK), hormone receptor signaling pathways (progesterone receptor), Cyclooxygenase-2 and Her-2 are considered as key factors involved in the onset and maintenance of therapeutic resistance, suggesting that resistance is a multi-factorial phenomenon.

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“…Another perspective for this issue derives from studies showing that, in colorectal cancer patients, aberrations in the KRAS/BRAF axis often coexist with aberrations in the PI3K/AKT/mTOR axis (83)(84)(85), with each being a resistance pathway for the other (86,87). These co-mutations occur in other cancers as well, but not as frequently.…”

Section: Role Of the Pi3k/akt/mtor Axismentioning

confidence: 99%

Genomically Driven Tumors and Actionability across Histologies:BRAF-Mutant Cancers as a Paradigm

Turski¹,

Vidwans²,

Janků

et al. 2016

Molecular Cancer Therapeutics

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The diagnosis, classification, and management of cancer are traditionally dictated by the site of tumor origin, for example, breast or lung, and by specific histologic subtypes of site-oforigin cancers (e.g., non-small cell versus small cell lung cancer). However, with the advent of sequencing technologies allowing for rapid, low cost, and accurate sequencing of clinical samples, new observations suggest an expanded or different approach to the diagnosis and treatment of cancer-one driven by the unique molecular features of the tumor. We discuss a genomically driven strategy for cancer treatment using BRAF as an example. Several key points are highlighted: (i) molecular aberrations can be shared across cancers; (ii) approximately 15% of all cancers harbor BRAF mutations; and (iii) BRAF inhibitors, while approved only for melanoma, have reported activity across numerous cancers and related disease types bearing BRAF aberrations. However, BRAF-mutated colorectal cancer has shown poor response rate to BRAF inhibitor monotherapy, striking a cautionary note. Yet, even in this case, emerging data suggest BRAF-mutated colorectal cancers can respond well to BRAF inhibitors, albeit when administered in combination with other agents that impact resistance pathways. Taken together, these data suggest that molecular aberrations may be the basis for a new nosology for cancer. Mol Cancer Ther; 15(4); 533-47. Ó2016 AACR.

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Patterns of PIK3CA alterations in familial colorectal and endometrial carcinoma

Cited by 61 publications

References 35 publications

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population

Resistance to chemotherapy and hormone therapy in endometrial cancer

Genomically Driven Tumors and Actionability across Histologies:BRAF-Mutant Cancers as a Paradigm

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