These findings were consistent with those reported for SUMMIT hormone receptor-positive (HR+) HER2-mutant mBC cohorts, in which patients treated with N or N + fulvestrant (N+F) experienced promising clinical responses but shorter DOR. Although limited by small numbers, addition of T to N in patients with HER2-mutant mTNBC, despite deepening and prolonging response, did not appear to preclude eventual emergence of either on-pathway (ERBB3) or off-pathway (KRAS, TP53) mutations. In contrast to observations in N+F+T-treated patients with HR+, HER2-mutant disease, no additional HER2 alterations were detected upon progression in N+T-treated patients with mTNBC in this small dataset. Future investigations may evaluate clinical utility of sequencing therapies targeted to mutations acquired in response to N-based therapy in patients with HER2-mutant mTNBC.

2 months ago

Clinical • Combination therapy • Genomic analysis • Circulating tumor DNA • Metastases • Omic analysis

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • mTOR (Mechanistic target of rapamycin kinase)

TP53 mutation • KRAS mutation • HR positive • HER-2 amplification • HER-2 mutation • KRAS Q61H • ERBB3 mutation • MTOR mutation • HER-2 T798I • TP53 R196*

MSK-ACCESS

Herceptin (trastuzumab) • Nerlynx (neratinib) • fulvestrant

9ms

Uterine Leiomyosarcoma Associated With Perivascular Epithelioid Cell Tumor: A Phenomenon of Differentiation/Dedifferentiation and Evidence Suggesting Cell-of-Origin. (PubMed, Am J Surg Pathol)

We hypothesize that LMSs containing smooth muscle progenitor cells may give rise to divergent, lineage-specific PEComatous lesions through differentiation or dedifferentiation. While we do not dispute the recognition of PEComas as a distinct entity, we advocate the hypothesis that modified smooth muscle cells represent the origin of a subset of PEComas, and our case series provides evidence to suggest this theory.

9 months ago

Journal

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • FH (Fumarate Hydratase) • GPNMB (Glycoprotein Nmb) • CTSK (Cathepsin K)

TP53 mutation • RB1 expression • TP53 expression • TP53 R196*

11ms

Li-Fraumeni syndrome presenting with de novo TP53 mutation, severe phenotype and advanced paternal age: a case report. (PubMed, Hered Cancer Clin Pract)

Advanced paternal age is a risk factor to consider when hereditary cancer syndrome is suspected. Early detection of hereditary cancer syndromes and their multi-disciplinary surveillance and treatment is important to improve clinical outcomes for these patients. Further investigation of the relationship between the pathogenic variant of TP53 and its phenotype may guide the stratification of surveillance and treatment.

11 months ago

Journal • Metastases

TP53 (Tumor protein P53)

TP53 mutation • TP53 R196*

1year

Epithelial-to-mesenchymal transition status correlated with ultrastructural features, and TP53 mutation in patient-derived oral cancer cell lines. (PubMed, Mol Biol Rep)

Cellular migratory properties are associated with cellular ultrastructure, epithelial-to-mesenchymal transition status and the status of TP53 mutation in the genome.

1 year ago

Preclinical • Journal

TP53 (Tumor protein P53) • CDH1 (Cadherin 1) • VIM (Vimentin) • TWIST1 (Twist Family BHLH Transcription Factor 1) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)

TP53 mutation • TP53 wild-type • CDH1 expression • VIM expression • TP53 amplification • ZEB1 expression • TP53 R196*

over1year

The molecular signature of gain-of-function (GOF) vs. non-GOF classification TP53 mutations in colorectal cancer. (ASCO 2023)

In CRC, non-GOF mTP53 was prevalent in more than half of all cases. Compared to GOF mTP53, predictive biomarkers of response to immune checkpoint inhibitors (TMB and MSI-H/dMMR) were higher in this cohort albeit still relatively rare. Otherwise, differences in molecular signatures between GOF and non-GOF mTP53 did not contain clinically meaningful differences.

over 1 year ago

Tumor mutational burden • MSi-H Biomarker • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • BCL2L1 (BCL2-like 1) • BAX (BCL2-associated X protein) • CDC25C (Cell Division Cycle 25C) • CDK1 (Cyclin-dependent kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • BBC3 (BCL2 Binding Component 3) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)

TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • BRAF mutation • TP53 wild-type • MYC expression • TP53 R175H • BAX expression • TP53 R248Q • TP53 R273H • TP53 G245S • TP53 R196* • TP53 R213 • TP53 R273C

MI Tumor Seek™

almost2years

Molecular characterization of advanced primary cardiac sarcomas (Sarcoma-RC 2023)

All patients gained clinical benefit by first-line doxorubicin-based chemotherapy (2 partial responses, 2 stable disease), although disease control was short-lived (<10 months)...The somatic NGS analysis was consistent with the genomic profile of soft tissue sarcomas and cfDNA analysis was demonstrated for the first time in this rare tumor type to be a potential tool for dynamic tracking of clinical outcome. Legal entity responsible for the study The authors.

almost 2 years ago

Tumor mutational burden • BRCA Biomarker • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor) • MTAP (Methylthioadenosine Phosphorylase) • MDM2 (E3 ubiquitin protein ligase) • KMT2D (Lysine Methyltransferase 2D) • PTCH1 (Patched 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TSC2 (TSC complex subunit 2) • NOTCH2 (Notch 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • NOTCH3 (Notch Receptor 3) • EP300 (E1A binding protein p300) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • IRS2 (Insulin receptor substrate 2) • MAPK1 (Mitogen-activated protein kinase 1) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • CCND3 (Cyclin D3) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • CTNNA1 (Catenin Alpha 1) • EPHB4 (EPH receptor B4) • RAD52 (RAD52 Homolog DNA Repair Protein) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • ALOX12B (Arachidonate 12-Lipoxygenase) • FANCC (FA Complementation Group C) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)

TMB-L • MDM2 amplification • RET mutation • MET mutation • PTCH1 mutation • FANCA mutation • TSC2 mutation • TP53 R196*

FoundationOne® CDx

doxorubicin hydrochloride

over2years

Undifferentiated embryonal sarcoma of the liver occurring in an adolescent: a case report with genomic analysis. (PubMed, Surg Case Rep)

A UESL should be considered in the differential diagnosis of large and well-defined solid liver lesions. Although the prognosis of UESL is extremely unfavorable, aggressive surgical resection with adjuvant chemotherapy and genomic analysis may be helpful for ensuring long-term survival.

over 2 years ago

Journal

TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11)

TP53 mutation • STK11 mutation • TP53 R196*

FoundationOne® CDx

ifosfamide • etoposide IV

over3years

Sodium Stibogluconate in the MDS/AML With One of the 65 Defined p53 Mutations (clinicaltrials.gov)

P2, N=5, Recruiting, First Affiliated Hospital of Jinan University

over 3 years ago

New P2 trial

TP53 (Tumor protein P53)

TP53 mutation • TP53 K139N • TP53 R196* • TP53 R213

Lenocta (sodium stibogluconate)

over3years

[VIRTUAL] Circulating tumor DNA-based genomic profiling of small bowel adenocarcinoma. (ASCO 2021)

This study represents the first large-scale blood-based ctDNA genomic profiling of SBA . SBA represents a unique molecular entity with differences in frequency and types of GA compared to CRC . Variations in GA were noted based on anatomic origin within the small intestine .

over 3 years ago

BRCA Biomarker • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • CDK4 (Cyclin-dependent kinase 4) • APC (APC Regulator Of WNT Signaling Pathway) • BRCA (Breast cancer early onset) • CDK6 (Cyclin-dependent kinase 6) • GNAS (GNAS Complex Locus) • MAPK3 (Mitogen-Activated Protein Kinase 3)

TP53 mutation • BRAF V600E • HER-2 mutation • NF1 mutation • APC mutation • BRAF amplification • TP53 R196*

Guardant360® CDx