Reference Detail

Ref Type

Journal Article

PMID

(29636477)

Authors

Chen L, Yang L, Yao L, Kuang XY, Zuo WJ, Li S, Qiao F, Liu YR, Cao ZG, Zhou SL, Zhou XY, Yang WT, Shi JX, Huang W, Hu X, Shao ZM

Title

Characterization of PIK3CA and PIK3R1 somatic mutations in Chinese breast cancer patients.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Nature communications	9	1	2018 Apr 10	1357	Nat Commun

URL

Abstract Text

Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the development and progression of tumors. Here, we determine that somatic mutations in PIK3CA (44%), PIK3R1 (17%), AKT3 (15%), and PTEN (12%) are prevalent and diverse in Chinese breast cancer patients, with 60 novel mutations identified. A high proportion of tumors harbors multiple mutations, especially PIK3CA plus PIK3R1 mutations (9.0%). Next, we develop a recombination-based mutation barcoding (ReMB) library for impactful mutations conferring clonal advantage in proliferation and drug responses. The highest-ranking PIK3CA and PIK3R1 mutations include previously reported deleterious mutations, as well as mutations with unknown significance. These PIK3CA and PIK3R1 impactful mutations exhibit a mutually exclusive pattern, leading to oncogenesis and hyperactivity of PI3K pathway. The PIK3CA impactful mutations are tightly associated with hormone receptor positivity. Collectively, these findings advance our understanding of PI3K impactful mutations in breast cancer and have important implications for PI3K-targeted therapy in precision oncology.

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Molecular Profile	Treatment Approach
No data available in table

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role
No data available in table

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
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Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
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Showing 1 to 9 of 9 entries

Gene	Variant	Impact	Protein Effect	Variant Description
PIK3CA	E39K	missense	gain of function - predicted	PIK3CA E39K lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). E39K results in increased cell proliferation and transformation ability in culture (PMID: 29533785, PMID: 29636477), and therefore, is predicted to lead to a gain of Pik3ca protein function.
PIK3CA	K51N	missense	no effect - predicted	PIK3CA K51N lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). K51N results in proliferation similar to wild-type Pik3ca in culture (PMID: 29636477), and therefore, is predicted to have no effect on Pik3ca protein function.
PIK3CA	E80K	missense	unknown	PIK3CA E80K lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). E80K has been identified in the scientific literature (PMID: 29636477, PMID: 22722201, PMID: 31174159), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2025).
PIK3CA	N345I	missense	gain of function - predicted	PIK3CA N345I lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N345I results in increased cell survival, but was not transforming in cell culture in one study (PMID: 26627007), but in two other studies, demonstrated increased transformation ability in multiple cell lines compared to wild-type Pik3ca in culture (PMID: 29533785, PMID: 29636477), and therefore, is predicted to lead to a gain of Pik3ca protein function.
PIK3CA	N457K	missense	unknown	PIK3CA N457K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N457K has been identified in the scientific literature (PMID: 29636477, PMID: 19844788), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2024).
PIK3CA	D538Y	missense	no effect - predicted	PIK3CA D538Y lies within the PIK helical domain of the Pik3ca protein (UniProt.org). D538Y results in cell growth levels similar to wild-type Pik3ca in culture (PMID: 29636477), and therefore, is predicted to have no effect on Pik3ca protein function.
PIK3CA	E710G	missense	no effect - predicted	PIK3CA E710G does not lie within any known functional domains of the Pik3ca protein (UniProt.org). E710G results in cell growth levels similar to wild-type Pik3ca in culture (PMID: 29636477), and therefore, is predicted to have no effect on Pik3ca protein function.
PIK3CA	N1044Y	missense	unknown	PIK3CA N1044Y lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). N1044Y has been identified in the scientific literature (PMID: 29636477, PMID: 27191687, PMID: 27548314), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Feb 2025).
PIK3CA	H1047T	missense	unknown	PIK3CA H1047T is a hotspot mutation that lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1047T has identified in the scientific literature (PMID: 29636477), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2024).

Showing 1 to 9 of 9 entries

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Showing 1 to 6 of 6 entries

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PIK3CA E39K	breast cancer	resistant	Buparlisib	Preclinical - Cell culture	Actionable	In a preclinical study, breast cancer cells expressing PIK3CA E39K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477).	29636477
PIK3CA E453K	breast cancer	resistant	Buparlisib	Preclinical - Cell culture	Actionable	In a preclinical study, breast cancer cells expressing PIK3CA E453K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477).	29636477
PIK3CA E542K	breast cancer	resistant	Buparlisib	Preclinical - Cell culture	Actionable	In a preclinical study, breast cancer cells expressing PIK3CA E542K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477).	29636477
PIK3CA E545K	breast cancer	resistant	Buparlisib	Preclinical - Cell culture	Actionable	In a preclinical study, breast cancer cells expressing PIK3CA E545K demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477).	29636477
PIK3CA G1049R	breast cancer	resistant	Buparlisib	Preclinical - Cell culture	Actionable	In a preclinical study, breast cancer cells expressing PIK3CA G1049R demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477).	29636477
PIK3CA N345I	breast cancer	resistant	Buparlisib	Preclinical - Cell culture	Actionable	In a preclinical study, breast cancer cells expressing PIK3CA N345I demonstrated resistance to treatment with Buparlisib (BKM120) in culture (PMID: 29636477).	29636477

Showing 1 to 6 of 6 entries

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