Nickolas Papadopoulos
A5037021577- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Monoclonal and Polyclonal Antibodies Research
- Colorectal Cancer Treatments and Studies
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Genetic and Kidney Cyst Diseases
- Immunotherapy and Immune Responses
- Bladder and Urothelial Cancer Treatments
- Salivary Gland Tumors Diagnosis and Treatment
- Tumors and Oncological Cases
- Virus-based gene therapy research
- Nephrotoxicity and Medicinal Plants
- CAR-T cell therapy research
- Genomic variations and chromosomal abnormalities
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Ovarian cancer diagnosis and treatment
- Pancreatic function and diabetes
- Colorectal Cancer Surgical Treatments
- Advanced Biosensing Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Cancer Cells and Metastasis
- DNA Repair Mechanisms
Cancer Genetics (United States)
2016-2025
Johns Hopkins University
2016-2025
Sidney Kimmel Comprehensive Cancer Center
2016-2025
Sidney Kimmel Cancer Center
2016-2025
Johns Hopkins Medicine
2015-2024
Cancer Research Center
2014-2024
Howard Hughes Medical Institute
2014-2024
Bloomberg (United States)
2019-2024
University of Baltimore
2017-2024
Lustgarten Foundation
2020
Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic due mismatch-repair defects may be susceptible immune checkpoint blockade.We conducted phase 2 study evaluate clinical activity pembrolizumab, an anti-programmed death 1 inhibitor, in 41 patients progressive metastatic carcinoma or without deficiency. Pembrolizumab was administered intravenously at dose 10 mg per kilogram body weight every 14 days...
The genomes of cancers deficient in mismatch repair contain exceptionally high numbers somatic mutations. In a proof-of-concept study, we previously showed that colorectal with deficiency were sensitive to immune checkpoint blockade antibodies programmed death receptor-1 (PD-1). We have now expanded this study evaluate the efficacy PD-1 patients advanced repair-deficient across 12 different tumor types. Objective radiographic responses observed 53% patients, and complete achieved 21%...
The development of noninvasive methods to detect and monitor tumors continues be a major challenge in oncology. We used digital polymerase chain reaction-based technologies evaluate the ability circulating tumor DNA (ctDNA) 640 patients with various cancer types. found that ctDNA was detectable >75% advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, head neck cancers, but less than 50% primary brain, renal, prostate, or thyroid cancers. In...
There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease urgently needed. Toward end, we performed a comprehensive genetic analysis 24 cancers. We first determined sequences 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, searched homozygous deletions amplifications tumor DNA by using microarrays containing probes approximately 10(6) single-nucleotide polymorphisms....
The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers unprecedented detail. To begin a systematic analysis such alterations, we determined well-annotated protein-coding genes two common tumor types. Analysis 13,023 11 breast and colorectal revealed that individual tumors accumulate an average approximately 90 mutant but only subset these contribute neoplastic process. Using stringent criteria delineate this subset, identified 189...
Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast colorectal tumors determined sequences genes Reference Sequence database these samples. Based on analysis exons representing 20,857 transcripts 18,191 genes, conclude genomic landscapes cancers are composed a handful commonly mutated gene "mountains" much larger number "hills" at low frequency. We describe...
Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common types through assessment of the levels circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, 1005 patients with nonmetastatic, clinically detected cancers ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive median 70% types. The sensitivities ranged from 69 98% for five (ovary, esophagus)...
Recent studies have shown that a locus responsible for hereditary nonpolyposis colorectal cancer (HNPCC) is on chromosome 2p and tumors developing in these patients contain alterations microsatellite sequences (RER+ phenotype). We used microdissection to obtain highly polymorphic markers from 2p16. These other were ordered panel of somatic cell hybrids define 0.8 Mb interval containing the HNPCC locus. Candidate genes then mapped, one was found lie within interval. identified this candidate...
Some cases of hereditary nonpolyposis colorectal cancer (HNPCC) are due to alterations in a mutS -related mismatch repair gene. A search large database expressed sequence tags derived from random complementary DNA clones revealed three additional human genes, all related the bacterial mutL One these genes ( hMLH1 ) resides on chromosome 3p21, within 1 centimorgan markers previously linked susceptibility HNPCC kindreds. Mutations that would disrupt gene product were identified such kindreds,...
The mutational profile of head and neck cancer is complex may pose challenges to the development targeted therapies.
Pancreatic neuroendocrine tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis PanNETs, we determined exomic sequences 10 nonfamilial PanNETs and then screened most commonly mutated genes in 58 additional PanNETs. The frequently specify proteins implicated chromatin remodeling: 44% had somatic inactivating mutations MEN1, which encodes menin, component histone methyltransferase complex, 43% encoding either two subunits...
We examined the immune microenvironment of primary colorectal cancer using immunohistochemistry, laser capture microdissection/qRT-PCR, flow cytometry, and functional analysis tumor-infiltrating lymphocytes. A subset displayed high infiltration with activated CD8(+) cytotoxic T lymphocyte (CTL) as well Th1 cells characterized by IFNγ production transcription factor TBET. Parallel tumor genotypes revealed that virtually all tumors this active Th1/CTL had defects in mismatch repair, evidenced...
Malignant cells, like all actively growing must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the binding proteins alpha thalassemia/mental retardation syndrome X-linked ( ATRX ) or death-domain associated protein DAXX shown to underlie a mechanism not involving telomerase (alternative lengthening telomeres), and point promoter reverse transcriptase TERT gene increase expression...
Detection of circulating tumor DNA in patients with resected stage II colon cancer provides evidence residual disease.
Ovarian clear cell carcinoma (OCCC) is an aggressive human cancer that generally resistant to therapy. To explore the genetic origin of OCCC, we determined exomic sequences eight tumors after immunoaffinity purification cells. Through comparative analyses normal cells from same patients, identified four genes were mutated in at least two tumors. PIK3CA, which encodes a subunit phosphatidylinositol-3 kinase, and KRAS, well-known oncoprotein, had previously been implicated OCCC. The other...
Turcot's syndrome is characterized clinically by the concurrence of a primary brain tumor and multiple colorectal adenomas. We attempted to define at molecular level.
A subset of sporadic colorectal tumors and most developing in hereditary nonpolyposis cancer patients display frequent alterations microsatellite sequences. Such have been thought to manifest replication errors (RER+), but the basis for has remained conjectural. We demonstrate that mutation rate (CA)n repeats RER+ tumor cells is at least 100-fold RER- show by vitro assay increased mutability associated with a profound defect strand-specific mismatch repair. This deficiency was observed...
The proteins encoded by ATRX and DAXX participate in chromatin remodeling at telomeres other genomic sites. Because inactivating mutations of these genes are common human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status tumors. We found that 61% PanNETs displayed abnormal characteristic a telomerase-independent maintenance mechanism termed ALT (alternative lengthening telomeres). All exhibiting had or loss nuclear protein. also correlate with central nervous...
Desperately Seeking Glucose Mutations in oncogenes and tumor suppressor genes allow cancer cells to outgrow their neighboring healthy cells. What microenvironmental conditions provide a selective growth advantage these cells? Yun et al. (p. 1555 , published online 6 August) identify low glucose availability as factor driving the acquisition of KRAS oncogenic mutations that survive grow. In genetically matched colorectal differed only mutational status oncogene, mutant selectively...
Getting all stressed out by vitamin C Few experimental cancer therapies have incited as much debate C. Yet the mechanistic effect of on cells is still poorly understood. Yun et al. studied human colorectal with KRAS or BRAF mutations and found that they “handle” in a different way than other cells, ultimately to their detriment (see Perspective Reczek Chandel). Because certain receptor up-regulated mutant take up oxidized form (dehydroascorbate). This leads oxidative stress, inactivation...
A mutation in the gene GNAS serves as a marker for pancreatic cysts that can progress to become invasive adenocarcinomas, guiding therapy.
More than 2% of adults harbor a pancreatic cyst, subset which progresses to invasive lesions with lethal consequences. To assess the genomic landscapes neoplastic cysts pancreas, we determined exomic sequences DNA from epithelium eight surgically resected each major cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), cystic (MCNs), and solid pseudopapillary (SPNs). SPNs are low-grade malignancies, IPMNs MCNs, but not SCAs, have capacity progress cancer....