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Gene | PIK3CA |
Variant | N345K |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | PIK3CA N345K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). N345K results in increased phosphorylation of Akt, activation of downstream signaling, increased cell proliferation and migration, and is transforming in cell culture (PMID: 17376864, PMID: 29533785, PMID: 34779417). |
Associated Drug Resistance | |
Category Variants Paths |
PIK3CA mutant PIK3CA act mut PIK3CA N345K PIK3CA mutant PIK3CA exon5 PIK3CA N345K |
Transcript | NM_006218.4 |
gDNA | chr3:g.179203765T>G |
cDNA | c.1035T>G |
Protein | p.N345K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011512894 | chr3:g.179203765T>G | c.1035T>G | p.N345K | RefSeq | GRCh38/hg38 |
XM_011512894.2 | chr3:g.179203765T>G | c.1035T>G | p.N345K | RefSeq | GRCh38/hg38 |
XM_006713658 | chr3:g.179203765T>G | c.1035T>G | p.N345K | RefSeq | GRCh38/hg38 |
NM_006218 | chr3:g.179203765T>G | c.1035T>G | p.N345K | RefSeq | GRCh38/hg38 |
NM_006218.3 | chr3:g.179203765T>G | c.1035T>G | p.N345K | RefSeq | GRCh38/hg38 |
XM_006713658.5 | chr3:g.179203765T>G | c.1035T>G | p.N345K | RefSeq | GRCh38/hg38 |
NM_006218.4 | chr3:g.179203765T>G | c.1035T>G | p.N345K | RefSeq | GRCh38/hg38 |
XM_006713658.4 | chr3:g.179203765T>G | c.1035T>G | p.N345K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
PIK3CA N345K | breast cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). | 26627007 |
PIK3CA N345K | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited survival of transformed cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). | 26627007 |
PIK3CA N345K | breast cancer | sensitive | Dactolisib | Preclinical | Actionable | In a preclinical study, BEZ235 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). | 26627007 |
PIK3CA N345K | breast cancer | sensitive | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, Alpelisib (BYL719) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). | 26627007 |
PIK3CA N345K | head and neck squamous cell carcinoma | predicted - sensitive | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with Piqray (alpelisib) resulted in inhibition of proliferation and increased apoptosis in a head and neck squamous cell carcinoma cell line expressing PIK3CA N345K in culture (PMID: 34779417). | 34779417 |
PIK3CA N345K | breast cancer | sensitive | Lapatinib | Preclinical | Actionable | In a preclinical study, Tykerb (lapatinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). | 26627007 |
PIK3CA N345K | breast cancer | sensitive | MK2206 | Preclinical | Actionable | In a preclinical study, MK2206 inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). | 26627007 |
PIK3CA N345K | breast cancer | sensitive | Neratinib | Preclinical | Actionable | In a preclinical study, Nerlynx (neratinib) inhibited survival of transformed breast epithelial cell lines overexpressing PIK3CA N345K in culture (PMID: 26627007). | 26627007 |
PIK3CA N345K | endometrial mixed adenocarcinoma | no benefit | Copanlisib | Case Reports/Case Series | Actionable | In a Phase II (NRG-GY008) trial, Aliqopa (copanlisib) was well tolerated but demonstrated limited efficacy, resulted in stable disease in a patient with endometrial mixed adenocarcinoma harboring PIK3CA N345K (PMID: 31934607). | 31934607 |
PIK3CA N345K | lung squamous cell carcinoma | no benefit | Taselisib | Case Reports/Case Series | Actionable | In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in no response in two patients harboring PIK3CA N345K (PMID: 31158500; NCT02785913). | 31158500 |