A5048060846- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Science, Research, and Medicine
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Gastric Cancer Management and Outcomes
- Cancer, Hypoxia, and Metabolism
- Health Systems, Economic Evaluations, Quality of Life
- CRISPR and Genetic Engineering
- Lung Cancer Research Studies
- Renal and related cancers
- Lymphoma Diagnosis and Treatment
- Esophageal Cancer Research and Treatment
- Chronic Lymphocytic Leukemia Research
- Genomic variations and chromosomal abnormalities
- Cancer-related Molecular Pathways
- Prostate Cancer Treatment and Research
- Renal cell carcinoma treatment
- Neuroendocrine Tumor Research Advances
- Epigenetics and DNA Methylation
- Cancer therapeutics and mechanisms
- Cancer Cells and Metastasis
- Glioma Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
Memorial Sloan Kettering Cancer Center
2015-2024
Kettering University
2015-2024
HistoGenetics (United States)
2017
New York Proton Center
2017
University of California, Los Angeles
2010-2011
Cancer Genetics (United States)
2004
Columbia University
2004
Tata Memorial Hospital
1990-1998
The prognosis of patients with glioblastoma (GBM) remains dismal, a median survival approximately 15 months. Current preclinical GBM models are limited by the lack "normal" human microenvironment and inability many tumor cell lines to accurately reproduce biology. To address these limitations, we have established model system whereby can retro-engineer patient-specific GBMs using patient-derived glioma stem cells (GSCs) embryonic (hESC)-derived cerebral organoids. Our organoid (GLICO) shows...
Although p53 inactivation promotes genomic instability
Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear renal that have no standard therapy. The oncogenic drivers in these tumours are unknown. Here we perform molecular analysis 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA single-nucleotide polymorphism array, fluorescence situ hybridization, immunohistochemistry and cell-based assays. We identify recurrent somatic mutations 29 genes, including NF2...
The anti-HER2 antibody trastuzumab is standard care for advanced esophagogastric (EG) cancer with ERBB2 (HER2) amplification or overexpression, but intrinsic and acquired resistance are common. We conducted a phase II study of afatinib, an irreversible pan-HER kinase inhibitor, in trastuzumab-resistant EG cancer. analyzed pretreatment tumor biopsies and, select cases, performed comprehensive characterization postmortem metastatic specimens following acquisition drug resistance. Afatinib...
Chromophobe renal cell carcinoma (chRCC) typically shows ~7 chromosome losses (1, 2, 6, 10, 13, 17, and 21) ~31 exonic somatic mutations, yet carries ~5%-10% metastatic incidence. Since extensive chromosomal can generate proteotoxic stress compromise cellular proliferation, it is intriguing how chRCC, a tumor with low number of develop lethal metastases. Genomic features distinguishing from nonmetastatic chRCC are unknown. An integrated approach, including whole-genome sequencing (WGS),...
Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, shRNA, shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness vivo, led to a DNA methylation transcriptional profile resembling IDH1 mutant LGAs. The differentiation block was caused by silencing of the transcription factor SOX2 secondary disassociation its...
Myoepithelial carcinoma (MECA) is an aggressive salivary gland cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which associated overexpression. find FGFR1-PLAG1 seven (18%) cases, novel TGFBR3-PLAG1 fusion six (15%) cases. promotes tumorigenic phenotype vitro, absent...
With the combination of KRASG12C and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, patient samples, we detected heterogeneous pattern putative alterations expected primarily to prevent inhibition ERK signaling by drugs at progression. Serial analysis blood samples on treatment demonstrates that most these are low frequency except for amplification, recurrent mechanism...
Epigenetic modifications control cancer development and clonal evolution in various types. Here, we show that loss of the male-specific histone demethylase lysine-specific 5D (KDM5D) encoded on Y chromosome epigenetically modifies methylation marks alters gene expression, resulting aggressive prostate cancer. Fluorescent situ hybridization demonstrated segmental or total deletion cells is one causes decreased KDM5D mRNA expression. The result ChIP-sequencing analysis revealed preferably...
Copy number alterations (CNAs) play an important role in molding the genomes of breast cancers and have been shown to be clinically useful for prognostic therapeutic purposes. However, our knowledge intra-tumoral genetic heterogeneity this class somatic is limited. Here, using single-cell sequencing, we comprehensively map out facets copy alteration a cohort cancer tumors. Ou/var/www/html/elife/12-05-2020/backup/r analyses reveal: non-tumor cells (i.e. stroma) within tumor mass; extent which...
Secretory carcinoma of the breast (SCB) is a rare histological type with generally indolent clinical behaviour. We aim to elucidate clinical, pathological and molecular findings SCB cases identify characteristics associated aggressive courses.Fourteen patients were identified, including 12 women two men, median age 56 years (range = 8-81 years). Clinical data, diagnosis, follow-up reviewed. Eight presented palpable masses four radiographic abnormalities. All unilateral. Surgical procedures...
Abstract Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that typically associated with tobacco exposure and inactivation of RB1 TP53 genes. Here, we performed detailed clinicopathologic, genomic, transcriptomic profiling an atypical subset SCLC lacked co-inactivation arose in never/light smokers. We found most cases were chromothripsis—massive, localized chromosome shattering—recurrently involving 11 or 12 resulting extrachromosomal amplification CCND1 co-amplification...
Accurate determination of HER2/neu status in breast carcinoma is essential. Alteration preanalytic variables known to affect results. American Society Clinical Oncology (ASCO) and the College Pathologists (CAP) issued guidelines standardize fixation for increased accuracy. We studied effects changing on immunohistochemical fluorescence situ hybridization (FISH) results a HER2/neu+ invasive carcinoma. The clinical specimen was processed according ASCO/CAP guidelines, with remaining tumor...
Microcephaly and medulloblastoma may both result from mutations that compromise genomic stability. We report ATR, which is mutated in the microcephalic disorder Seckel syndrome, sustains cerebellar growth by maintaining chromosomal integrity during postnatal neurogenesis. Atr deletion granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis hypoplasia mice. Co-deletions of either or Bax Bak prevented Atr-deleted CGNPs, but failed to fully...
Radial glia (RG) cells are the first neural stem to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like with typical RG morphology and markers. The exhibit classic unique mitotic behavior normal in cell-autonomous manner. Single-cell RNA sequencing analyses glioblastoma reveal transcriptionally dynamic clusters that share profiles fetal radial reside quiescent cycling states. Functional assays show role for interleukin triggering exit from...