PTEN

Overview

PTEN is a phosphatase tumor suppressor antagonizing PI3K-AKT signaling; loss-of-function alterations are pervasive across many cancers.

Alterations observed in the corpus

  • Identified as one of eight significantly mutated genes in GBM, with mutations or deletions in 36% of cases; part of the RTK/RAS/PI3K pathway which is altered in 88% of samples PMID:18772890.
  • PTEN was included in LUAD pathway/metastasis analyses in the MSK-CHORD clinicogenomic dataset (n=24,950) PMID:39506116.
  • PTEN truncating mutations/deletions in 17% of RT-OS (osteosarcoma) vs 14% sporadic OS (n=12 RT-OS, n=76 sporadic OS); frequencies were similar between RT and sporadic settings PMID:37350195.
  • PTEN recurrent driver mutations enriched in MG3/MG4 (hypermetabolic/proliferative) molecular groups of meningioma; novel driver identified at 3–5% frequency collectively with KDM6A and CHD2 (Fisher exact P = 0.002) PMID:34433969.
  • PTEN mutations in 7% of cervical cancers (N=177); enriched in adenosquamous histology (14%) PMID:37643132.
  • PTEN mutations less frequent in Black endometrial carcinoma patients compared to White patients (26% vs. 55%); associated with endometrioid histology and PI3K pathway activation; the lower frequency in Black patients contributes to reduced eligibility for PI3K/AKT/mTOR pathway-targeted trials PMID:37651310.
  • PTEN deletions/mutations in 12% of STLMS and 18% of ULMS; PTEN deletions co-occurred with RB1 deletions in ULMS; associated with worse PFS in STLMS PMID:38488807.
  • PTEN deep deletions prevalent across prostate cancer PDXs; some models showed PTEN expression loss without deep deletion or mutation, implicating other regulatory mechanisms PMID:38488813.
  • PTEN mutated in 76% of dMMR/MSI-H gynecologic cancers treated with nivolumab; not associated with clinical benefit or resistance to PD-1 blockade PMID:38653864.
  • PTEN detected as ctDNA alteration in the pan-cancer liquid biopsy VTE risk study (N=4,141 discovery cohort); in multivariate analysis individual gene-level alterations were not independently associated with VTE after controlling for ctDNA detection status PMID:39147831.
  • Homozygous PTEN deletion observed in one myxoid/round-cell liposarcoma (MRLS) tumor with high phospho-AKT; a splice-site PTEN mutation observed in one pleomorphic liposarcoma (PLLS); variably elevated PTEN in kinase-domain PIK3CA mutants may explain their attenuated AKT activation relative to helical-domain mutants in 207 high-grade sarcomas (sarc_mskcc) PMID:20601955.
  • Mutations correlated with copy number loss in LUAD; associated with lower overall mutation rates; part of mTOR pathway alterations (>30% of tumours). PMID:18948947
  • Mutated in 10% of a longitudinal African breast cancer cohort PMID:36585450
  • PTEN R142W detected at resistance to KRASG12C + EGFR inhibition in CRC PMID:36355783
  • PTEN assessed in gallbladder carcinoma (GBC) genomic landscape study PMID:36228155
  • Frequently deleted and mutated in prostate cancer; identified as a key altered gene in integrative genomic profiling of 218 tumors PMID:20579941
  • Mutated in pancreatic neuroendocrine tumors (PanNET) identified by exome sequencing PMID:21252315
  • Among the most frequently mutated genes in high-grade serous ovarian carcinoma (HGSOC) in TCGA integrated genomic analysis PMID:21720365
  • PTEN loss-of-function mutations detected in HNSCC whole-exome sequencing (74 tumor-normal pairs, Broad), activating the PI3K pathway PMID:21798893
  • PTEN mutation and deletion status were characterized across 947 cancer cell lines in the CCLE pharmacogenomic profiling study, with PTEN loss correlating with sensitivity to PI3K/AKT pathway inhibitors PMID:22460905
  • Somatic mutations and homozygous deletions in 7.7% (5/65) of TNBC; copy number losses in 3% of cases PMID:22495314
  • Homozygous deletions identified as rare but potentially significant events in breast cancer across METABRIC cohort (2,000 tumors) PMID:22522925
  • Recurrently mutated and deleted in prostate cancer; inversely associated with SPOP mutations in primary tumors (P = 0.044) PMID:22610119
  • Recurrently disrupted by structural rearrangements in 4/25 melanoma tumors; PREX2 is a known PTEN-interacting protein and negative regulator of PTEN activity PMID:22622578
  • Inactivating mutations leading to AKT activation identified in breast cancer WES (100 tumors, Sanger cohort) PMID:22722201
  • Functional loss via MAGI3 disruption in breast cancer (Broad WES/WGS, 103 tumors); MAGI3 PDZ domain required for PTEN inhibition of PI3K; MAGI3-AKT3 fusion disrupts this interaction in triple-negative breast cancer PMID:22722202
  • Focal deletion and mutation in SHH-subgroup medulloblastoma (PCGP WGS, 37 tumors); previously reported alteration confirmed in this cohort PMID:22722829
  • Loss and mutations identified as a significantly mutated gene in CRPC (Michigan WES, 112 tumors); interaction network identified PMID:22722839
  • Deletions/mutations in 4% of non-hypermutated colorectal tumors; mutually exclusive with PIK3CA and PIK3R1 alterations in 276-tumor TCGA CRC cohort PMID:22810696
  • Mutation/focal deletion co-occurring with BRAF in 44% of melanomas and rarely with NRAS (4%, p=4.9e-5); identified as significantly mutated by InVEx in 121-tumor Broad WES cohort PMID:22817889
  • Copy loss at 10q23 frequent in BRAF/NRAS-mutant class of melanomas in the 147-tumor Yale WES cohort PMID:22842228
  • PTEN deletion in 4% (3/74) of colorectal cancer tumors (Genentech WES) PMID:22895193
  • PTEN inactivating missense mutations in 3/29 (10%) of SCLC tumors (CLCGP); loss of phosphatase activity activating PI3K pathway PMID:22941188
  • PTEN inactivating mutations in 2-4% of SCLC tumors with hotspot mutations and copy-number loss (JHU WES/WGS, 36 tumors) PMID:22941189
  • PTEN mutation and deletion in lung squamous cell carcinoma (TCGA, 178 tumors); part of 47% PI3K pathway alteration rate PMID:22960745
  • PTEN alterations identified in lung adenocarcinoma (Broad WES, 183 tumors) as part of PI3K pathway dysregulation PMID:22980975
  • Loss more common in Basal-like breast cancer; activates PI3K pathway; mutually exclusive with PIK3CA, PIK3R1, and AKT1 mutations (P=0.025) in 510 TCGA breast tumors (brca_tcga_pub) PMID:23000897
  • PI3K pathway dependence (involving PTEN loss) confirmed in hypodiploid ALL; PI3K inhibitors GDC-0941 and BEZ235 substantially inhibited proliferation of all hypodiploid ALL tumors ex vivo (all_stjude_2013, 124 pediatric cases) PMID:23334668
  • Mutated in 4/145 EAC tumors; part of PI3K-pathway alterations alongside PIK3CA and PIK3R1 PMID:23525077
  • Recurrently subclonal deletion in prostate cancer (p=10⁻⁵ vs NKX3-1 clonality); disrupted by chromoplexy in 9 cases; co-deleted with PIK3R1 in one chain, indicating PI3K-pathway convergence via structural rearrangement PMID:23622249
  • Mutated in 84% of MSS endometrioid and 94% of POLE-ultramutated endometrial tumors; only 11% in serous-like; co-occurs with TP53 in endometrioid (50%) but rarely in serous (2.6%) PMID:23636398
  • PTEN R130fs and K144Q mutations (both in catalytic domain) co-occurring in one ACC tumor; part of the recurrently altered PI3K/AKT axis in adenoid cystic carcinoma PMID:23685749
  • Among the top eight SMGs in ccRCC (q<0.00001); PTEN mutation enriched in m3 mRNA subtype (11% vs 1%, p<0.0001) in TCGA 450-case analysis PMID:23792563
  • Deletion in 4% of high-grade bladder tumors; deleted samples showed reduced PTEN mRNA expression PMID:23897969
  • Mutation/deletion mutually exclusive with PI3K mutations (p=0.0047) in GBM; combined PTEN/PI3K pathway alterations in 59.4% of GBM PMID:24120142
  • PI3K pathway alteration in intrahepatic cholangiocarcinoma (IHCH); part of the 22% aggregate PI3K pathway alteration rate in the discovery-screen cohort alongside PIK3CA, PIK3C2A, and PIK3C2G PMID:24185509
  • Missense mutations (11 patients; 9 in phosphatase domain), nonsense R233*, frameshift Y86fs, and a copy-number deletion (Patient 36) in BRAF-inhibitor-resistant melanoma; combined RAF + PI3K inhibition was synergistic in PTEN-null A2058 cells PMID:24265153
  • Somatic mutation in 2/23 (9%) pancreatic acinar cell carcinomas PMID:24293293
  • TMZ-associated missense mutations A121T and G165R acquired in patient 24’s second low-grade glioma recurrence; both residues are critical to phosphatase activity and are recurrently mutated in GBM PMID:24336570
  • Single frameshift mutation p.Arg11LysfsTer32 co-occurring with EWSR1::MYB fusion in a metatypical adenoid cystic carcinoma of the sphenoid sinus PMID:24418857
  • Homozygous deletion in RMS2117 rhabdomyosarcoma sample; loss of PTEN activates the PI3K/AKT axis, a recurrent oncogenic mechanism in RMS PMID:24436047
  • PTEN parallel evolution previously demonstrated across spatially separated tumor regions in ccRCC (EV001/EV002), illustrating intratumor heterogeneity PMID:24487277
  • PTEN harbors inactivating mutations in ESCC, contributing to PI3K pathway activation PMID:24686850
  • PTEN loss contributes to PI3K/AKT pathway hyperactivation in HCC; part of the oncogenic signaling landscape analyzed in the HCC precision-medicine genomic framework PMID:24798001
  • PTEN focal copy number loss in prostate cancer; independently associated with biochemical recurrence (HR=3.04, P=0.001) but CNA burden remains prognostic after adjusting for it PMID:25024180
  • PTEN PI3K pathway loss in gastric cancer (EGC); PTEN focally deleted in CIN subtype PMID:25079317
  • PTEN recurrent mutations in 6% of muscle-invasive bladder cancer (BLCA); part of PI3K/AKT pathway alterations PMID:25092538
  • Nonsilent somatic mutation in 6/66 (9%) plus 2 homozygous deletions in ChRCC; MutSig q<0.1; germline PTEN mutations underlie Cowden syndrome predisposing to ChRCC PMID:25155756
  • Private PI3K-pathway event of unknown significance in paired primary/metastasis CRC cohort; PI3K-pathway heterogeneity clinically relevant given active PI3K inhibitor development and evidence PIK3CA mutations may predict aspirin benefit PMID:25164765
  • Homozygous deletion of gene or promoter in 6/7 patient-derived CRPC organoid lines; biallelic loss in all CRPC lines; near-universal loss supports prioritizing PTEN/PI3K-pathway-directed therapy in CRPC PMID:25201530
  • Missense/nonsense/frameshift mutations in 9/22 (41%) uterine/ovarian carcinosarcoma cases; co-occurs with PIK3CA; PI3K pathway hits support trials of PI3K/mTOR/AKT inhibitors PMID:25233892
  • Significantly mutated in chromophobe renal cell carcinoma (chRCC) in a non-clear-cell RCC (nccRCC) multisubtype WES study PMID:25401301
  • PTEN focal deletions in 2 PTC tumors; 5 tumors showed PTEN loss through 10q23.31 deletions; PI3K/PPARγ pathway alterations including PTEN, AKT1/2, and PAX8/PPARG fusions found in 4.5% (18/402) of PTCs. PMID:25417114
  • PTEN identified as a driver gene in HBV-associated intrahepatic cholangiocarcinoma (iCCA) cohort; loss contributes to PI3K/AKT pathway dysregulation in CCA. PMID:25526346
  • PI3K/RAS negative regulator with inactivating events in 1–3 of 29 metastatic cSCC samples; component of the mTOR-dependent alteration axis associated with shorter PFS PMID:25589618
  • Mutated/altered in 2% of HNSCC; component of RTK/RAS/PI(3)K pathway altered in 62% of HPV(−) and 61% of HPV(+) tumours PMID:25631445
  • In HCC, PTEN is a component of the PI3K/AKT/mTOR pathway altered in 51% of cases. PMID:25822088
  • In mCRPC, PTEN biallelic loss occurs in 40.7% of cases; it is the most common PI3K pathway alteration and co-occurs with PIK3CB activating mutations. PMID:26000489
  • In cutaneous melanoma (SKCM), PTEN mutations and deletions are enriched in BRAF-mutant tumors. PMID:26091043
  • Confirmed accessory tumour suppressor in SCLC; validated in mouse models (previously known role in murine SCLC). PMID:26168399
  • Homozygous deletion (6%) and somatic mutation (7%) in invasive lobular carcinoma (ILC), mutually exclusive with PIK3CA; combined PTEN inactivation rate 14% in LumA ILC vs 3% LumA IDC (p=9E-4) PMID:26451490
  • Homozygous deletion in 15% of primary prostate tumors (highest rates among TCGA tumor types); total alteration rate 17%; preferentially co-occurs with ERG fusion PMID:26544944
  • 10q23.3 deletion in 5/25 (20%) Sézary syndrome; functionally connected to recurrent PREX2 mutations that inhibit PTEN PMID:26551667
  • Mutated in n=168 diffuse gliomas (LGG/GBM) across TCGA multi-platform dataset; recovered as a known glioma driver PMID:26824661
  • PTEN mutated as part of the PI3K/AKT/mTOR pathway, disrupted in 39% ATC vs 11% PDTC (P=1×10⁻³); NF1 truncating mutations co-occurred with PTEN truncation in 3 BRAF/RAS-WT ATCs (P=2×10⁻³). PMID:26878173
  • PTEN mutation unique to the plasmacytoid component of a mixed bladder tumor (alongside CDH1 Y68fs), supporting branched clonal evolution within the plasmacytoid variant. PMID:26901067
  • PTEN homozygous CN loss assessed for site-distribution analysis in mCRPC; no metastatic-site association was detected. PMID:26928463
  • Only one homozygous PTEN deletion observed (in the non-responding group) in 38 anti-PD-1-treated metastatic melanoma patients (WES); cohort was underpowered to confirm the Peng et al. 2015 PTEN-loss/immunotherapy-resistance association. PMID:26997480
  • Confirmed as a significantly mutated gene (pan-cancer tumor suppressor) in 619-case colorectal carcinoma WES cohort (NHS/HPFS); newly statistically designated as a CRC driver gene by virtue of cohort size. PTEN+10q23.1 deletion LOH coupling also noted in the METABRIC breast cancer cohort. PMID:27149842
  • Not highlighted as a significantly mutated gene in the 1,144-tumor NSCLC landscape study but referenced in the broader RTK/Ras/Raf pathway context; PI3K pathway alterations including PTEN inactivation contribute to oncogene-negative lung ADC. PMID:27158780
  • Identified as a Mut-driver in the METABRIC 2,433-tumor breast cancer cohort (Akt-signaling pathway TSG); PTEN + 10q23.1 deletion co-occurrence (OR=3.4) confirms classic two-hit inactivation; 15/57 PTEN-mutant tumors also carried recurrent PIK3CA mutations. PMID:27161491
  • PTEN loss-of-function mutations (n=5) plus missense VUS (n=4) detected in a germ cell tumor cohort; PI3K/mTOR pathway alterations as actionable targets for cisplatin-resistant patients PMID:27646943.
  • PTEN alteration prompted PI3K-inhibitor trial enrollment in a recurrent/metastatic head and neck cancer NGS cohort PMID:27442865.
  • Mutated in uRCC, falling within the mTORC1-hyperactive subset alongside MTOR, TSC1, and TSC2 mutations; mutually exclusive with other mTORC1-pathway alterations across 62 uRCC cases PMID:27713405
  • Listed as a significantly mutated driver in HR+/HER2− metastatic breast cancer, also recurrent in early breast cancer PMID:28027327
  • PI3K-pathway alteration enriched in ESCC2 subtype alongside PIK3CA and PIK3R1; part of 24% PI3K-activating-alteration frequency in ESCCs in a multi-platform GEA genomic study PMID:28052061
  • Partial loss via 10q deletion observed on methylation-derived copy-number profile in an EWSR1::BEND2 bladder sarcoma; flagged as potentially actionable (PI3K/AKT/mTOR pathway; possible mTOR-inhibitor or PARP-inhibitor sensitivity) but not pursued therapeutically PMID:28199314
  • 6 inactivating mutations in a prospective LUAD cohort (860 patients, MSK-IMPACT); classified as unmatched driver alteration PMID:28336552
  • Focal deletion in primary tumors only in ALM (34 patients, WGS); additionally a PTEN::RPL11 fusion identified in a single tumor with no other PTEN alterations PMID:28373299
  • Recurrent low-VAF oncogenic mutations in endometrial polyps (WGS, 23 polyps); co-occurring with PIK3CA, PIK3R1, ERBB2, PPP2R1A, and FBXW7; supports classification of a subset of polyps as precursor lesions to UCEC PMID:28445112
  • Deletion in 1/19 (5%) of cases in the 1p/19q FISH false-positive subgroup with glioblastoma-like NGS signature in anaplastic oligodendroglioma cohort PMID:28472509
  • Assessed within 7-gene cross-histology panel in clear-cell endometrial carcinoma (CCEC); mutationally enriched in UEC-like profiles as part of the 34.9% of CCECs with PI3K-pathway alterations PMID:28485815
  • Altered in 79/500 (15.8%) in the MET500 pan-cancer metastatic cohort; also recurrently disrupted by fusions (n=11) PMID:28783718
  • Frequency rises sharply with castration resistance in prostate cancer (12% noncastrate → 29% mCRPC), co-occurring with RB1 loss; convergent PTEN+RB1 co-loss characterizes advanced mCRPC PMID:28825054
  • Recurrent rearrangements targeting PTEN identified in medulloblastoma (pan-MB WGS/WES cohort, n=491) PMID:28726821
  • PTEN shows a CRISPR-enriched (tumor-suppressor) pattern in DLBCL PMID:28985567
  • PTEN reviewed for homozygous CN loss in metastatic melanoma treated with nivolumab; no significant association with response to nivolumab was reported PMID:29033130
  • PTEN deletions (81% combined deep+shallow) and mutations (5%) in sarcoma; PI3K/AKT/MTOR pathway alterations in 84% of ULMS+STLMS C1 vs 44% of STLMS C2; nominates dual PI3K/MTOR or TORC1/TORC2 inhibitors PMID:29100075
  • Altered in 35% of MSI-H vs 5% of MSS mCRC (p<0.01) in a cohort of 1,640 metastatic colorectal tumors PMID:29316426
  • Listed among antigen-presentation and immunology genes profiled in the MSK-IMPACT NSCLC cohort evaluating TMB and anti-PD-(L)1 response (n=240) PMID:29337640
  • Referenced from prior targeted-panel literature as recurrent in HPV(−) vulvar SCC; not identified as a new finding in this 15-tumor WES cohort PMID:29422544
  • Confirmed as a KIRC SMG by both MutSig2CV and MuSiC2 in the MC3 pan-cancer open-access MAF (10,510 TCGA tumor/normal pairs, 33 cancer types) PMID:29596782.
  • Homozygous loss or truncating mutation in 16% of 1,013 prostate tumors (prad_p1000); PTEN alteration is enriched in metastatic vs. primary PRAD and is part of the genomic signature proposed for prospective risk stratification PMID:29610475.

Cancer types (linked)

  • LUAD / NSCLC — pathway/metastasis analyses in MSK-CHORD PMID:39506116.
  • OS — PTEN truncating mutations/deletions at similar frequency in RT-OS (17%) and sporadic OS (14%) PMID:37350195.
  • Meningioma (MNG) — novel driver in MG3/MG4 molecular groups (3–5% frequency) PMID:34433969.
  • Cervical cancer (CESC) — mutations in 7%; enriched in adenosquamous carcinoma PMID:37643132.
  • Endometrial carcinoma (UCEC) — less frequent in Black patients (26% vs. 55%); highest frequency biomarker of the endometrioid/PI3K subtype PMID:37651310; mutated in 76% of dMMR gynecologic cancers, not predictive of nivolumab response PMID:38653864.
  • Leiomyosarcoma (STLMS / ULMS) — deletions/mutations in 12–18%; co-occurring with RB1 deletions in ULMS PMID:38488807.
  • Prostate cancer (PRAD) — deep deletions prevalent in PDX models; expression loss also through non-genomic mechanisms PMID:38488813.

Co-occurrence and mutual exclusivity

  • Not specifically reported in the corpus.

Therapeutic relevance

  • Not directly therapeutically targeted in the corpus.

Open questions

  • None flagged.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15. - PMID:29033130

This page was processed by wiki-cli on 2026-05-15. - PMID:29100075

This page was processed by wiki-cli on 2026-05-15. - PMID:29316426

This page was processed by wiki-cli on 2026-05-15. - PMID:29337640

This page was processed by wiki-cli on 2026-05-15. - PMID:29422544

This page was processed by entity-page-writer on 2026-05-15. - PMID:29596782

This page was processed by wiki-cli on 2026-05-15. - PMID:29610475

This page was processed by wiki-cli on 2026-05-15.