Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

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 Nature communications
Vol 9
Issue 1
Date 2018 Apr 10
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.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
PIK3CA D538Y missense no effect - predicted PIK3CA D538Y lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). D538Y did not result in increased cell proliferation in culture compared to wild-type Pik3ca and therefore, is predicted to have no effect on Pik3ca protein function (PMID: 29636477).
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 result in a gain of Pik3ca protein function.
PIK3CA E710G missense no effect - predicted PIK3CA E710G lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). E710G did not result in increased cell proliferation in culture compared to wild-type Pik3ca and therefore, is predicted to have no effect on Pik3ca protein function (PMID: 29636477).
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, Sep 2020).
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, Apr 2020).
PIK3CA K51N missense no effect - predicted PIK3CA K51N lies within the PI3K-ABD domain of the Pik3ca protein (UniProt.org). K51N did not result in increased cell proliferation in culture compared to wild-type Pik3ca and therefore, is predicted to have no effect on Pik3ca protein function (PMID: 29636477).
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, Sep 2020).
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, N345I demonstrated increased transformation ability in multiple cell lines compared to wild-type Pik3ca (PMID: 29533785, PMID: 29636477), and therefore, is predicted to result in 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, Sep 2020).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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
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