A5084980524- Sarcoma Diagnosis and Treatment
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Chromatin Remodeling and Cancer
- Bone Tumor Diagnosis and Treatments
- Cancer-related Molecular Pathways
- Tumors and Oncological Cases
- MicroRNA in disease regulation
- Cancer-related gene regulation
- Genomic variations and chromosomal abnormalities
- Neurogenetic and Muscular Disorders Research
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- Bioinformatics and Genomic Networks
- Muscle Physiology and Disorders
- Immune Cell Function and Interaction
- Vascular Tumors and Angiosarcomas
- Hedgehog Signaling Pathway Studies
- Oral and Maxillofacial Pathology
- Bone health and treatments
- RNA Research and Splicing
Lunenfeld-Tanenbaum Research Institute
2014-2024
Mount Sinai Hospital
2007-2024
Sinai Health System
2018-2024
University of Toronto
1999-2021
National Institutes of Health
2015
National Cancer Institute
2015
Leidos (United States)
2015
Frederick National Laboratory for Cancer Research
2015
Universidad de Navarra
2015
Children's Hospital at Montefiore
2015
Looping together genes in cancer A subset of human cancers are characterized by aberrant fusion two specific genes. In some cases, the activity resultant protein drives tumor growth. Most appear to arise from simple reciprocal chromosomal translocations. Anderson et al. found that characteristic gene a bone and soft tissue called Ewing sarcoma is produced far more complicated mechanism (see Perspective Imielinski Ladanyi). nearly half tumors examined, was created formation dramatic genomic...
The etiologic contribution of germline genetic variation to sporadic osteosarcoma is not well understood. Osteosarcoma a sentinel cancer Li-Fraumeni syndrome (LFS), in which approximately 70% families meeting the classic criteria have TP53 mutations. We sequenced exons 765 cases. Data were analyzed with χ2 tests, logistic regression, and Cox proportional hazards regression models. observed high frequency young cases (age <30 years) carrying known LFS- or likely LFS-associated mutation (3.8%)...
Metastasis is the leading cause of death in patients with osteosarcoma, most common pediatric bone malignancy. We conducted a multistage genome-wide association study osteosarcoma metastasis at diagnosis 935 to determine whether germline genetic variation contributes risk metastasis. identified an SNP, rs7034162, NFIB significantly associated European cases, as well cases African and Brazilian ancestry (meta-analysis all cases: P = 1.2 × 10(-9); OR, 2.43; 95% confidence interval, 1.83-3.24)....
Mutations of the TP53 gene have been associated with resistance to chemotherapy as well poor prognosis in many different malignancies. This is first prospective study prognostic value somatic mutations patients newly diagnosed extremity osteosarcoma.One hundred ninety-six high-grade, nonmetastatic osteosarcoma extremities were enrolled from seven tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 44 months). All received neoadjuvant or...
The chromosomal region 12q13-15 is recurrently amplified in osteosarcoma (OS), but its importance bone tumor development remains unknown. Although there are two major candidate genes (MDM2, a TP53 downregulator, and CDK4, involved cell cycle progression) considered to be the driving this region, size of amplicon number have not been determined. In study, we used 130 classical OS 15 parosteal determine MDM2 CDK4 amplification frequency OS. Tumors which these were map correlation with clinical...
BACKGROUND In some malignancies, p53 mutations are associated with tumor progression. To address the role of in development and progression osteosarcoma, authors analyzed specimens from 247 patients primary localized osteosarcomas 25 that were metastatic at time diagnosis. The group included 27 matched biopsy-resection 21 biopsy-metastasis paired specimens. METHODS examined nature location (exons 4–10) by polymerase chain reaction–single-strand conformation polymorphism confirmed direct DNA...
We carried out whole genome and transcriptome sequencing on four tumour/normal pairs of epithelioid sarcoma. These index cases were supplemented with three additional tumours cell lines. Unlike rhabdoid tumour (the other major group SMARCB1-negative cancers), sarcoma shows a complex higher mutational rate, comparable to that ovarian carcinoma. Despite this burden, SMARCB1 mutations remain the most frequently recurring event are probably critical drivers formation. Several show heterozygous...
Amplification of several genes that map to a region chromosome 17p11.2, including COPS3, was observed in high-grade osteosarcoma. These were also shown be overexpressed and may involved osteosarcoma tumorigenesis. COPS3 encodes subunit the COP9 signalosome implicated ubiquitination ultimately degradation P53 tumor suppressor. To determine relation between amplification, mutation, patient outcome osteosarcoma, tumors from large cohort patients with long-term clinical follow-up...
Despite the importance of Hedgehog signaling in bone development, relationship between pathway expression and osteosarcoma clinical characteristics outcome has not been investigated. In this study 43 high-grade human samples, we detected high levels ligand gene, IHH, target genes, PTCH1 GLI1, most samples. Further analysis tumors patients with localized disease at diagnosis identified coexpression IHH exclusively large tumors. Higher were observed more frequently males higher GLI1 responsive...
Immune checkpoint proteins, such as PD-L1 and PD-1, are important in several cancers; however, their role osteosarcoma (OSA) soft tissue sarcoma (STS) remains unclear. Our aims were to determine whether subsets of OSA/STS harbor tumor-infiltrating lymphocytes (TILs) express PD-L1, how expression is related clinical outcome. Tissue sections 25 cases each untreated undifferentiated pleomorphic (UPS), myxofibrosarcoma (MFS), liposarcoma (LPS) 24 leiomyosarcoma (LMS) subjected...
Survival rates for osteosarcoma, the most common primary bone cancer, have changed little over past three decades and are particularly low patients with metastatic disease. We conducted a multi‐institutional genome‐wide association study (GWAS) to identify germline genetic variants associated overall survival in 632 including 523 of European ancestry 109 from Brazil. time‐to‐event analysis estimated hazard ratios (HR) 95% confidence intervals (CI) using Cox proportional hazards models,...
There are limited data regarding the molecular characterization of undifferentiated pleomorphic sarcomas (UPS; formerly malignant fibrous histiocytoma). This study aimed to investigate utility next generation sequencing (NGS) in UPS identify subsets patients who harbour actionable mutations. Patients diagnosed with underwent pathological re‐evaluation by a pathologist specializing sarcoma. Tumor DNA was isolated from archived fresh frozen tissue samples and genotyped using NGS Illumina MiSeq...
Soft-tissue sarcomas (STS) are rare malignancies showing lineage differentiation toward diverse mesenchymal tissues. Half of all high-grade STSs develop lung metastasis with a median survival 15 months. Here, we used genetically engineered mouse model that mimics undifferentiated pleomorphic sarcoma (UPS) to study the molecular mechanisms driving metastasis. High-grade were generated Cre recombinase technology using mice conditional mutations in
: Sarcomas are a heterogeneous group of cancers, many with high rates recurrence and metastasis, leading to significant morbidity mortality. Due lack early diagnostic biomarkers, by the time recurrent disease can be clinically detected, it is often extensive difficult treat. Here, we sought investigate methods detecting ctDNA in sarcoma patient plasma potentially monitor recurrence, progression, response treatment.
Abstract Osteosarcoma, fibrous dysplasia, and myositis ossificans contain osteoid‐producing cells that are not necessarily morphologically typical osteoblasts. Nevertheless, these pathologic may share differentiation steps with osteoblasts at the molecular level. Osteocalcin, a bone‐specific extracellular matrix protein, is marker of mature Osteocalcin upregulated by transcription factor core‐binding alpha 1, which responsible for commitment to osteoblastic lineage, downregulated MSX2,...
// Philip Wong 1,2,3 , Angela Hui 4 Jie Su 5 Shijun Yue Benjamin Haibe-Kains 4,12 Nalan Gokgoz 6 Wei Xu Jeff Bruce Justin Williams Charles Catton 1,2 Jay S. Wunder 6,7,8 Irene L. Andrulis 6,9,10 Rebecca Gladdy 6,8 Brendan Dickson 10,11 Brian O'Sullivan and Fei-Fei Liu 1,2,4,12 1 Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada 2 Department of Oncology, 3 Département Centre Hospitalier de L'Université Montréal, QC, Research Institute,...
AbstractIdentification of mutations causing cystic fibrosis (CF) in the Turkish population is essential for assessment molecular basis CF Turkey and development strategies prenatal diagnosis genetic counseling. Here, we present an updated report found from extensive screening study entire coding region, including exon-intron boundaries promoter region. Cases which could not be identified were also screened previously defined large alterations (TG)mTn-M470V loci. This revealed a total 27...