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Gene | PTEN |
Variant | T321fs |
Impact List | frameshift |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | PTEN T321fs results in a change in the amino acid sequence of the PTEN protein beginning at aa 321 of 403, likely resulting in premature truncation of the functional protein (UniProt.org). T321fs has not been characterized, however, due to the effects of other truncation mutations downstream of T321 (PMID: 10468583), is predicted to lead to a loss of Pten protein function. |
Associated Drug Resistance | |
Category Variants Paths |
PTEN mutant PTEN inact mut PTEN T321fs |
Transcript | NM_000314.8 |
gDNA | chr10:g.(87961052_87961053) |
cDNA | c.(961_960) |
Protein | p.T321fs |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000314 | chr10:g.(87961052_87961053) | c.(961_960) | p.T321fs | RefSeq | GRCh38/hg38 |
NM_000314.6 | chr10:g.(87961052_87961053) | c.(961_960) | p.T321fs | RefSeq | GRCh38/hg38 |
NM_000314.8 | chr10:g.(87961052_87961053) | c.(961_960) | p.T321fs | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 N550K PIK3CA I20M PIK3CA P539R PTEN R130Q PTEN T321fs | endometrial cancer | sensitive | Infigratinib + Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Truseltiq (infigratinib) and Pictilisib (GDC-0941) resulted in a synergistic effect, demonstrating inhibition of cell proliferation, decreased colony formation, and cell death in an endometrial cancer cell line harboring FGFR2 N550K, PIK3CA I20M and P539R, and PTEN R130Q and T321fs*23 in culture (PMID: 28119489). | 28119489 |
FGFR2 N550K PIK3CA I20M PIK3CA P539R PTEN R130Q PTEN T321fs | endometrial cancer | sensitive | Buparlisib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Truseltiq (infigratinib) and Buparlisib (BKM120) resulted in a synergistic effect, demonstrating inhibition of cell proliferation, decreased colony formation, and cell death in an endometrial cancer cell line harboring FGFR2 N550K, PIK3CA I20M and P539R, and PTEN R130Q and T321fs*23 in culture (PMID: 28119489). | 28119489 |
FGFR2 N550K PIK3CA I20M PIK3CA P539R PTEN R130Q PTEN T321fs | endometrial cancer | sensitive | Alpelisib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Truseltiq (infigratinib) and Alpelisib (BYL719) resulted in a synergistic effect, demonstrating inhibition of cell proliferation and induced cell death in an endometrial cancer cell line harboring FGFR2 N550K, PIK3CA I20M and P539R, and PTEN R130Q and T321fs*23 in culture (PMID: 28119489). | 28119489 |
KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 |
KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | resistant | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) demonstrated limited inhibition of Kit, Erk, and Mtor signaling and resulted in minimal (22.9%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 |
KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited Kit, Erk, and Mtor signaling, resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 |
KIT Y570_L576del KIT D816E PTEN T321fs | gastrointestinal stromal tumor | sensitive | Imatinib + LY294002 | Preclinical - Pdx | Actionable | In a preclinical study, Gleevec (imatinib mesylate) in combination with LY294002 resulted in enhanced tumor growth inhibition compared to monotherapy in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT D816E, KIT Y570_L576del, and PTEN T321fs, which was established from a patient who did not respond to Gleevec (imatinib mesylate), Sutent (sunitinib), and Nexavar (sorafenib) (PMID: 29100343). | 29100343 |