Janet C. Lindsey
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View article: Molecular and clinical heterogeneity within <i>MYC</i>-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study
Molecular and clinical heterogeneity within <i>MYC</i>-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study Open
Background MYC/MYCN are the most frequent oncogene amplifications in medulloblastoma (MB) and its primary biomarkers of high-risk (HR) disease. However, while many patients’ MYC(N)-amplified tumors are treatment-refractory, some achieve lo…
View article: MYC-dependent upregulation of the de novo serine and glycine synthesis pathway is a targetable metabolic vulnerability in group 3 medulloblastoma
MYC-dependent upregulation of the de novo serine and glycine synthesis pathway is a targetable metabolic vulnerability in group 3 medulloblastoma Open
Background Group 3 medulloblastoma (MBGRP3) represents around 25% of medulloblastomas and is strongly associated with c-MYC (MYC) amplification, which confers significantly worse patient survival. Although elevated MYC expression is a sign…
View article: MDB-66. HIGH-THROUGHPUT SMALL MOLECULE DRUG SCREENING, TRANSCRIPTOMICS AND INTEGRATIVE AI IDENTIFY TARGETABLE MYC-DEPENDENT THERAPEUTIC VULNERABILITIES IN HIGH-RISK MEDULLOBLASTOMA
MDB-66. HIGH-THROUGHPUT SMALL MOLECULE DRUG SCREENING, TRANSCRIPTOMICS AND INTEGRATIVE AI IDENTIFY TARGETABLE MYC-DEPENDENT THERAPEUTIC VULNERABILITIES IN HIGH-RISK MEDULLOBLASTOMA Open
INTRODUCTION MYC-amplified Group 3 medulloblastomas (MBGroup3-MYC) do not respond to conventional up-front therapies and are almost universally fatal (<5% survival). MYC is not directly targetable. Thus, the systematic development of th…
View article: MDB-74. SERINE/GLYCINE METABOLISM REPRESENTS A NOVEL TARGETABLE THERAPEUTIC VULNERABILITY IN MYC-AMPLIFIED MEDULLOBLASTOMA
MDB-74. SERINE/GLYCINE METABOLISM REPRESENTS A NOVEL TARGETABLE THERAPEUTIC VULNERABILITY IN MYC-AMPLIFIED MEDULLOBLASTOMA Open
BACKGROUND Medulloblastoma is the most frequent malignant brain tumour of childhood. Whilst advances in risk-stratification and upfront multimodal therapy have led to five-year survival rates around 70%, a subset of tumours remain refracto…
View article: OA14.04 Three-Year Outcomes with First-Line Pembrolizumab, in Patients with Non-Small-Cell Lung Cancer and A PD-L1 Tumor Proportion Score >90%
OA14.04 Three-Year Outcomes with First-Line Pembrolizumab, in Patients with Non-Small-Cell Lung Cancer and A PD-L1 Tumor Proportion Score >90% Open
View article: Supplementary Data from Rapid Diagnosis of Medulloblastoma Molecular Subgroups
Supplementary Data from Rapid Diagnosis of Medulloblastoma Molecular Subgroups Open
Supplementary Figures S1-S2; Supplementary Tables S1-S7.
View article: Data from Rapid Diagnosis of Medulloblastoma Molecular Subgroups
Data from Rapid Diagnosis of Medulloblastoma Molecular Subgroups Open
Purpose: Microarray studies indicate medulloblastoma comprises distinct molecular disease subgroups, which offer potential for improved clinical management.Experimental Design: Minimal mRNA expression signatures diagnostic fo…
View article: Data from Rapid Diagnosis of Medulloblastoma Molecular Subgroups
Data from Rapid Diagnosis of Medulloblastoma Molecular Subgroups Open
Purpose: Microarray studies indicate medulloblastoma comprises distinct molecular disease subgroups, which offer potential for improved clinical management.Experimental Design: Minimal mRNA expression signatures diagnostic fo…
View article: Supplementary Data from Rapid Diagnosis of Medulloblastoma Molecular Subgroups
Supplementary Data from Rapid Diagnosis of Medulloblastoma Molecular Subgroups Open
Supplementary Figures S1-S2; Supplementary Tables S1-S7.
View article: Medulloblastoma group 3 and 4 tumors comprise a clinically and biologically significant expression continuum reflecting human cerebellar development
Medulloblastoma group 3 and 4 tumors comprise a clinically and biologically significant expression continuum reflecting human cerebellar development Open
Medulloblastoma is currently subclassified into distinct DNA methylation subgroups/subtypes with particular clinico-molecular features. Using RNA sequencing (RNA-seq) in large, well-annotated cohorts of medulloblastoma, we show that transc…
View article: Medulloblastoma Group 3 and 4 Tumors Comprise a Clinically and Biologically Significant Expression Continuum Reflecting Human Cerebellar Development
Medulloblastoma Group 3 and 4 Tumors Comprise a Clinically and Biologically Significant Expression Continuum Reflecting Human Cerebellar Development Open
Summary Medulloblastoma is currently sub-classified into distinct DNA methylation subgroups/subtypes with particular clinico-molecular features. Using RNA-seq in large well annotated cohorts of medulloblastoma we show that transcriptionall…
View article: MEDB-36. Clinical and molecular heterogeneity within<i>MYC</i> and<i>MYCN</i> amplified medulloblastoma
MEDB-36. Clinical and molecular heterogeneity within<i>MYC</i> and<i>MYCN</i> amplified medulloblastoma Open
MYC and MYCN are the most commonly amplified oncogenes in medulloblastoma. Their overall association with a poor prognosis has supported their adoption as high-risk disease biomarkers in trials. However, emerging evidence suggests that cer…
View article: MEDB-79. MYC-driven upregulation of the<i>de novo</i> serine and glycine pathway is a novel therapeutic target for Group 3 MYC-amplified Medulloblastoma
MEDB-79. MYC-driven upregulation of the<i>de novo</i> serine and glycine pathway is a novel therapeutic target for Group 3 MYC-amplified Medulloblastoma Open
Despite advances in the molecular sub-classification and risk-stratification of medulloblastoma (MB), a subset of tumours remain refractory to current multimodal therapies. Group 3 (MBGroup3) patients represent around 25% of MBs, and ampli…
View article: Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse
Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse Open
Background Less than 5% of medulloblastoma (MB) patients survive following failure of contemporary radiation-based therapies. Understanding the molecular drivers of medulloblastoma relapse (rMB) will be essential to improve outcomes. Initi…
View article: Advanced molecular pathology for rare tumours: A national feasibility study and model for centralised medulloblastoma diagnostics
Advanced molecular pathology for rare tumours: A national feasibility study and model for centralised medulloblastoma diagnostics Open
Aims Application of advanced molecular pathology in rare tumours is hindered by low sample numbers, access to specialised expertise/technologies and tissue/assay QC and rapid reporting requirements. We assessed the feasibility of co‐ordina…
View article: MBRS-33. TEMPORARY RESTORATION OF p53 ACTIVITY DURING FRACTIONATED RADIOTHERAPY IN A GROUP3 MEDULLOBLASTOMA GEMM REPRESENTS A POWERFUL TOOL FOR RADIOBIOLOGY STUDIES
MBRS-33. TEMPORARY RESTORATION OF p53 ACTIVITY DURING FRACTIONATED RADIOTHERAPY IN A GROUP3 MEDULLOBLASTOMA GEMM REPRESENTS A POWERFUL TOOL FOR RADIOBIOLOGY STUDIES Open
TP53 pathway alterations are well-described events in medulloblastoma (MB) and are predictive of poor clinical outcome. Alterations are rare at diagnosis in Group3 (Gr3) and Group4, but enriched in Sonic Hedgehog and WNT subgroups. However…
View article: MBRS-44. TIME, PATTERN AND OUTCOME OF MEDULLOBLASTOMA RELAPSE ARE ASSOCIATED WITH TUMOUR BIOLOGY AT DIAGNOSIS AND UPFRONT THERAPY: A COHORT STUDY
MBRS-44. TIME, PATTERN AND OUTCOME OF MEDULLOBLASTOMA RELAPSE ARE ASSOCIATED WITH TUMOUR BIOLOGY AT DIAGNOSIS AND UPFRONT THERAPY: A COHORT STUDY Open
Disease relapse occurs in ~30% of children with medulloblastoma, and is fatal in the majority. We sought to establish whether clinico-molecular characteristics at diagnosis are associated with the nature of relapse, subsequent disease-cour…
View article: MBRS-60. THE ACTIONABLE GENOMIC LANDSCAPE OF RELAPSED MEDULLOBLASTOMA IS DEFINED BY MAINTENANCE AND ACQUISITION OF DRIVER EVENTS
MBRS-60. THE ACTIONABLE GENOMIC LANDSCAPE OF RELAPSED MEDULLOBLASTOMA IS DEFINED BY MAINTENANCE AND ACQUISITION OF DRIVER EVENTS Open
Medulloblastoma relapse (rMB) occurs in 30–40% of patients and is almost universally fatal. Understanding the genomic landscape of rMB, and its relationship to disease characteristics at diagnosis, will be essential to underpin the develop…
View article: MBRS-57. IDENTIFICATION OF <i>MYC</i>-DEPENDENT THERAPEUTIC VULNERABILITIES FOR TARGETING GROUP 3 MEDULLOBLASTOMA
MBRS-57. IDENTIFICATION OF <i>MYC</i>-DEPENDENT THERAPEUTIC VULNERABILITIES FOR TARGETING GROUP 3 MEDULLOBLASTOMA Open
Group 3 medulloblastoma (MBGroup3) is a highly aggressive tumour characterised by MYC amplification and elevated expression (17% of MBGroup3). MYC amplification in MBGroup3 confers a dismal prognosis using standard therapies, and there is …
View article: Time, pattern, and outcome of medulloblastoma relapse and their association with tumour biology at diagnosis and therapy: a multicentre cohort study
Time, pattern, and outcome of medulloblastoma relapse and their association with tumour biology at diagnosis and therapy: a multicentre cohort study Open
View article: Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity
Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity Open
View article: The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second‐generation subtypes
The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second‐generation subtypes Open
Aims Biomarker‐driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub‐classify iMB, and proffer strategies for personalized, risk‐adapted therapies. Methods We characterized the iMB molecular l…
View article: Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of Group 3 and Group 4 subtypes
Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of Group 3 and Group 4 subtypes Open
View article: MBCL-30. SUBGROUP-DIRECTED CLINICAL AND MOLECULAR STRATIFICATION OF DISEASE RISK IN INFANT MEDULLOBLASTOMA
MBCL-30. SUBGROUP-DIRECTED CLINICAL AND MOLECULAR STRATIFICATION OF DISEASE RISK IN INFANT MEDULLOBLASTOMA Open
Understanding the specific molecular pathology of infant medulloblastoma (iMB) is urgently required to inform contemporary treatments, risk-stratification and clinical trials. Comprehensive analysis incorporating central clinical/ patholog…
View article: MBRS-37. IN VITRO MODELLING OF TUMOUR EVOLUTION AND RADIOTHERAPY RESISTANCE IN MEDULLOBLASTOMA
MBRS-37. IN VITRO MODELLING OF TUMOUR EVOLUTION AND RADIOTHERAPY RESISTANCE IN MEDULLOBLASTOMA Open
Medulloblastoma relapse occurs in 30-40% of patients, is almost universally fatal and accounts for ~10% of childhood cancer deaths. Acquisition of combined MYC/MYCN and TP53 defects occurs in 30% of recurrences following standard-upfront-t…
View article: MBRS-29. IN-VIVO METABOLITE PROFILES FOR THE NON-INVASIVE AND RAPID IDENTIFICATION OF MOLECULAR SUBGROUP IN MEDULLOBLASTOMA
MBRS-29. IN-VIVO METABOLITE PROFILES FOR THE NON-INVASIVE AND RAPID IDENTIFICATION OF MOLECULAR SUBGROUP IN MEDULLOBLASTOMA Open
Molecular subgroup is now influencing risk stratification and disease management in medulloblastoma. Tissue metabolite profiles have shown promise in identifying the four consensus subgroups. A smaller number of metabolites can be measured…
View article: Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours
Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours Open
The implementation of personalised medicine in childhood cancers has been limited by a lack of clinically validated multi-target sequencing approaches specific for paediatric solid tumours. In order to support innovative clinical trials in…
View article: Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures
Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures Open
View article: Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours
Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours Open
The implementation of personalised medicine in childhood cancers has been limited by a lack of clinically validated multi-target sequencing approaches specific for paediatric solid tumours. In order to support innovative clinical trials in…
View article: Differentiating mouse embryonic stem cells express markers of human endometrium
Differentiating mouse embryonic stem cells express markers of human endometrium Open
These findings demonstrate that mESCs have the capacity to express human endometrial cell markers and demonstrate potential differentiation pathways of endometrial precursor and mesenchymal stem cells, providing an in vitro system to model…