News - PTCH1 mutation

1year

A case of familial adenomatous polyposis in an adult male with Lynch-like syndrome (PubMed, Zhonghua Wei Chang Wai Ke Za Zhi)

The patient underwent laparoscopic total colectomy with abdominoperineal resection and end ileostomy, then received 4 cycles adjuvant chemotherapy of oxaliplatin with capecitabine. This patient was followed up to April 2024 and performed well without abnormalities in serum cancer biomarkers and radiological examinations.

1 year ago

Journal • Tumor mutational burden

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MLH1 (MutL homolog 1) • PTCH1 (Patched 1)

KRAS mutation • TMB-H • PIK3CA mutation • PTCH1 mutation • AKT1 mutation

capecitabine • oxaliplatin

1year

Phase 2 Trial of Topical Application of the Hedgehog Inhibitor Patidegib in Patients With Gorlin Syndrome. (PubMed, Br J Dermatol)

Patidegib Topical Gel warrants further clinical development.

1 year ago

P2 data • Journal

PTCH1 (Patched 1)

PTCH1 mutation

cyclopamine • saridegib oral (IPI 926 oral) • patidegib topical (SGT-610)

1year

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

1 year ago

Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

1year

The genomic landscape of papillary thyroid carcinoma on next-generation sequencing in patients undergoing total thyroidectomy. (PubMed, World J Surg)

This Indian study identified novel somatic mutations and fusion genes in PTC, revealing a distinct genomic landscape with implications in precision diagnostics and personalized therapies. NGS with intraoperative live sampling shows promise in prognostication and therapeutic optimization of advanced/metastatic PTC cases.

1 year ago

Journal • Next-generation sequencing

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • CDH1 (Cadherin 1)

BRAF mutation • PIK3CA mutation • ALK mutation • PTCH1 mutation

1year

Whole‑exome sequencing insights into synchronous bilateral breast cancer with discordant molecular subtypes. (PubMed, Oncol Lett)

Heterogeneity in the hormone receptor and HER2 status of SBBC poses unique therapeutic challenges. Future studies should aim to identify the optimal management strategy for this disease.

1 year ago

Journal • BRCA Biomarker • Discordant

HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • BRCA1 (Breast cancer 1, early onset) • KDR (Kinase insert domain receptor) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • FAT1 (FAT atypical cadherin 1) • SETBP1 (SET Binding Protein 1) • EBF1 (EBF Transcription Factor 1) • HNF1A (HNF1 Homeobox A) • ROBO2 (Roundabout Guidance Receptor 2) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)

BRCA1 mutation • HR negative • PTCH1 mutation

1year

Cutaneous Basal Cell Carcinoma In Situ: A Review of the World Literature. (PubMed, Cureus)

Genomic evaluation has been performed in neoplasms from one individual with cutaneous BCC in situ and metastatic BCC; like other variants of BCC, an aberration of the PTCH1 gene was observed. In contrast to his liver metastasis, the in situ carcinoma had a lower tumor mutational burden, lacked programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) amplification and had a distinct PTCH1 mutation, suggesting that the in situ BCC of his skin and the metastatic BCC of his liver were derived from different clones of cells.

1 year ago

Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • PTCH1 (Patched 1) • PD-L2 (Programmed Cell Death 1 Ligand 2)

TMB-L • PTCH1 mutation

1year

Understanding and managing locally advanced basal cell carcinoma: insights into pathogenesis, therapeutic strategies, and the role of hedgehog pathway inhibitors. (PubMed, Ital J Dermatol Venerol)

BCC is characterized by low immunogenicity, which hinders immune response and contributes to treatment challenges. Enhanced understanding of the epidemiology, risk factors, and pathogenesis of locally advanced BCC, along with the development of targeted therapeutic approaches such as hedgehog pathway inhibitors, is essential for effectively managing this prevalent carcinoma and improving patient outcomes.

1 year ago

Review • Journal • Metastases

PTCH1 (Patched 1) • SMO (Smoothened Frizzled Class Receptor)

PTCH1 mutation • SMO mutation

1year

Vitamin D as a Nutritional Neoadjuvant During Photodynamic Therapy of Basal Cell Carcinoma (clinicaltrials.gov)

P1, N=37, Completed, Case Comprehensive Cancer Center | Active, not recruiting --> Completed

1 year ago

Trial completion

PTCH1 (Patched 1)

PTCH1 mutation

1year

Exploration of the causative gene in a case of multiple nevoid basal cell carcinoma: A case report. (PubMed, Rare Tumors)

The mutated gene in this patient was determined to be the ELP1 gene located on chromosome 9. This patient's ELP1 gene mutation may contribute to the development of multiple nevoid basal cell carcinomas on the face.

1 year ago

Journal

PTCH1 (Patched 1) • SUFU (SUFU Negative Regulator Of Hedgehog Signaling)

PTCH1 mutation

1year

A071401: Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients with Progressive Meningiomas (clinicaltrials.gov)

P2, N=124, Recruiting, Alliance for Clinical Trials in Oncology | Trial completion date: Oct 2024 --> Jan 2028 | Trial primary completion date: Oct 2024 --> Jan 2026

1 year ago

Trial completion date • Trial primary completion date

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • PTCH1 (Patched 1) • CDK4 (Cyclin-dependent kinase 4) • NF2 (Neurofibromin 2) • SMO (Smoothened Frizzled Class Receptor) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)

PIK3CA mutation • PTEN mutation • CDKN2A mutation • PTCH1 mutation • NF2 mutation • AKT1 mutation • SMO mutation • PIK3CA mutation + PTEN mutation • CDK4 mutation

Verzenio (abemaciclib) • Truqap (capivasertib) • Erivedge (vismodegib) • GSK2256098

1year

Clinicopathological and molecular spectrum of patients with germline SUFU mutations: A case series. (PubMed, J Cutan Pathol)

Germline SUFU mutation carriers should be recognized as a distinct group of patients carrying specific health risks, independent of meeting the BCNS criteria. Phenotypic prediction based on the specific SUFU mutation seems unfeasible. It is of utmost importance that the less apparent MHIBCC phenotype is recognized, to provide (second generation) germline SUFU mutation carriers appropriate healthcare.

1 year ago

Journal

PTCH1 (Patched 1) • SUFU (SUFU Negative Regulator Of Hedgehog Signaling)

PTCH1 mutation • SUFU mutation

over1year

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (ESMO 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor pts was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

over 1 year ago

Clinical • Tumor mutational burden • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • TMB-H • MET amplification • ALK rearrangement • FGFR1 amplification • MDM2 amplification • PTCH1 mutation • BRCA mutation • FGFR3 amplification • PTCH1 rearrangement • NTRK fusion

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)