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Gene | TP53 |
Variant | Y220C |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | TP53 Y220C is a hotspot mutation that lies within the DNA-binding domain (PMID: 17401432). Y220C results in decreased DNA binding, reduced Tp53 transcriptional activity, leads to resistance to apoptosis and failure of G1 arrest in cell culture (PMID: 16861262, PMID: 23630318, PMID: 31395785). |
Associated Drug Resistance | |
Category Variants Paths |
TP53 mutant TP53 exon6 TP53 Y220C TP53 mutant TP53 inact mut TP53 Y220C |
Transcript | NM_000546.6 |
gDNA | chr17:g.7674872T>C |
cDNA | c.659A>G |
Protein | p.Y220C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001407270.1 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001126114.2 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001407268.1 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001126113.3 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001126114 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001126112.3 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001407266.1 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001126113.2 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_000546 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001126112.2 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_000546.5 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_000546.6 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001126114.3 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001126113 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001126112 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001407262.1 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
NM_001407264.1 | chr17:g.7674872T>C | c.659A>G | p.Y220C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
TP53 Y220C | hepatocellular carcinoma | sensitive | CP-31398 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with CP-31398 resulted in decreased proliferation, increased apoptosis, and cell-cycle arrest in a hepatocellular carcinoma cell line harboring TP53 Y220C in culture (PMID: 26250460). | 26250460 |
TP53 Y220C | lung non-small cell carcinoma | resistant | Seliciclib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung carcinoma cells overexpressing TP53 Y220C were resistant to Roscovotine (seliciclib) induced apoptosis in culture (PMID: 22862161). | 22862161 |
TP53 Y220C | lung non-small cell carcinoma | sensitive | SLMP53-2 | Preclinical - Cell culture | Actionable | In a preclinical study, SLMP53-2 inhibited growth of a non-small cell lung carcinoma cell line expressing TP53 Y220C in culture (PMID: 31405179). | 31405179 |
TP53 Y220C | breast ductal carcinoma | sensitive | SLMP53-2 | Preclinical - Cell culture | Actionable | In a preclinical study, SLMP53-2 treatment inhibited growth of a breast ductal carcinoma cell line harboring TP53 Y220C and resulted in increased expression of the Tp53 targets MDM2, p21, and KILLER and decreased expression of Survivin and VEGF in culture (PMID: 31405179). | 31405179 |
TP53 Y220C | hepatocellular carcinoma | sensitive | SLMP53-2 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with SLMP53-2 induced cell-cycle arrest and apoptosis and inhibited growth, and resulted in restored Tp53 transcriptional activity in a hepatocellular carcinoma cell line harboring TP53 Y220C in culture, and inhibited tumor growth in xenograft models (PMID: 31405179). | 31405179 |
TP53 Y220C | hepatocellular carcinoma | sensitive | SLMP53-2 + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of SLMP53-2 and Nexavar (sorafenib) inhibited growth of a hepatocellular carcinoma cell line harboring TP53 Y220C in culture, and resulted in increased inhibition compared to Nexavar (sorafenib) alone (PMID: 31405179). | 31405179 |
TP53 Y220C | stomach cancer | predicted - sensitive | PC14586 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PC14586 treatment reactivated Tp53 function, resulted in 80% tumor regression after 3 weeks in cell line xenograft models of gastric cancer harboring TP53 Y220C (AACR Annual Meeting Apr 2021, Session MS.LBA01, Abstract # LB006). | detail... |
TP53 Y220C | Advanced Solid Tumor | predicted - sensitive | PC14586 | Phase I | Actionable | In a Phase I trial, PC14586 treatment demonstrated safety and preliminary efficacy in patients with advanced solid tumors harboring TP53 Y220C, and resulted in 5 partial responses amongst 21 evaluable patients including confirmed partial responses in one small cell lung cancer and one breast cancer patient, and unconfirmed partial responses in one colorectal cancer and two prostate cancer patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |
TP53 Y220C | Advanced Solid Tumor | predicted - sensitive | PC14586 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PC14586 treatment reactivated Tp53 function and resulted in cell cycle arrest in cancer cell lines harboring TP53 Y220C in culture, and led to complete cure in 80% of syngeneic xenograft models (AACR Annual Meeting Apr 2021, Session MS.LBA01, Abstract # LB006). | detail... |
TP53 Y220C | lung small cell carcinoma | predicted - sensitive | PC14586 | Case Reports/Case Series | Actionable | In a Phase I trial, PC14586 treatment resulted in a partial response in a patient with small cell lung cancer harboring TP53 Y220C (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |
TP53 Y220C | breast cancer | predicted - sensitive | PC14586 | Case Reports/Case Series | Actionable | In a Phase I trial, PC14586 treatment resulted in a partial response in a patient with breast cancer harboring TP53 Y220C (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |
TP53 Y220C | colorectal cancer | predicted - sensitive | PC14586 | Case Reports/Case Series | Actionable | In a Phase I trial, PC14586 treatment resulted in an unconfirmed partial response in a patient with colorectal cancer harboring TP53 Y220C (J Clin Oncol 40,no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |
TP53 Y220C | prostate cancer | predicted - sensitive | PC14586 | Case Reports/Case Series | Actionable | In a Phase I trial, PC14586 treatment resulted in unconfirmed partial responses in two patients with prostate cancer harboring TP53 Y220C (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3003); NCT04585750). | detail... |