Patents by Inventor Victor Velculescu
Victor Velculescu has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20130196312Abstract: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalogue the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene “mountains” and a much larger number of gene “hills” that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.Type: ApplicationFiled: September 28, 2011Publication date: August 1, 2013Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Laura D. WOOD, Williams D. PARSONS, Sian JONES, Jimmy LIN, Tobias SJÖBLOM, Thomas BARBER, Giovanni PARMIGIANI, Victor VELCULESCU, Kenneth W. KINZLER, Bert VOGELSTEIN
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Patent number: 8394598Abstract: Protein kinases are important signaling molecules involved in tumorigenesis. Mutational analysis of the human tyrosine kinase gene family (98 genes) identified somatic alterations in -20% of colorectal cancers, with the majority of mutations occurring in NTRK3, FES, GUCY2F and a previously uncharacterized tyrosine kinase gene called MCCK/MLK4. Most alterations were in conserved residues affecting key regions of the kinase domain. These data represent a paradigm for the unbiased analysis of signal transducing genes in cancer and provide useful targets for therapeutic intervention.Type: GrantFiled: February 15, 2010Date of Patent: March 12, 2013Assignee: The Johns Hopkins UniversityInventors: Alberto Bardelli, Will Parsons, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
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Publication number: 20120202207Abstract: We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.Type: ApplicationFiled: March 6, 2012Publication date: August 9, 2012Applicants: DUKE UNIVERSITY, THE JOHNS HOPKINS UNIVERSITYInventors: Bert VOGELSTEIN, Kenneth W. KINZLER, D. Williams PARSONS, Xiaosong ZHANG, Jimmy Cheng-Ho LIN, Rebecca J. LEARY, Philipp ANGENENDT, Nickolas PAPADOPOULOS, Victor VELCULESCU, Giovanni PARMIGIANI, Rachel KARCHIN, Sian JONES, Hai YAN, Darell BIGNER, Chien-Tsun KUAN, Gregory J. RIGGINS
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Publication number: 20120115735Abstract: There are currently few therapeutic options for patients with pancreatic cancers and new insights into the pathogenesis of this lethal disease are urgently needed. To this end, we performed a comprehensive analysis of the genes altered in 24 pancreatic tumors. First, we determined the sequences of 23,781 transcripts, representing 20,583 protein-encoding genes, in DNA from these tumors. Second, we searched for homozygous deletions and amplifications using microarrays querying ˜one million single nucleotide polymorphisms in each sample. Third, we analyzed the transcriptomes of the same samples using SAGE and next-generation sequencing-by-synthesis technologies. We found that pancreatic cancers contain an average of 63 genetic alterations, of which 49 are point mutations, 8 are homozygous deletions, and 6 are amplifications. Further analyses revealed a core set of 12 regulatory processes or pathways that were each genetically altered in 70% to 100% of the samples.Type: ApplicationFiled: September 3, 2009Publication date: May 10, 2012Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Bert Vogelstein, Kenneth W. Kinzler, D. Williams Parsons, Sian Jones, Xiaosong Zhang, Jimmy Cheng-Ho Lin, Rebecca J. Leary, Philipp Angenendt, Nickolas Papadopoulos, Victor Velculescu, Giovanni Parmigiani, Rachel Karchin, Scott Kern, Ralph Hruban, James R. Eshleman, Michael Goggins, Alison Klein
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Publication number: 20120095086Abstract: Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast and gastric cancers. Fifteen mutations were nonsense, frameshift or splice site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the tyrosine phosphatase genes are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.Type: ApplicationFiled: October 18, 2011Publication date: April 19, 2012Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Zhenghe WANG, Victor VELCULESCU, Kenneth W. KINZLER, Bert VOGELSTEIN
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Publication number: 20120009573Abstract: Transcription in mammalian cells can be assessed at a genome-wide level, but it has been difficult to reliably determine whether individual transcripts are derived from the Plus- or Minus-strands of chromosomes. This distinction can be critical for understanding the relationship between known transcripts (sense) and the complementary antisense transcripts that may regulate them. Here we describe a technique that can be used to (i) identify the DNA strand of origin for any particular RNA transcript and (ii) quantify the number of sense and antisense transcripts from expressed genes at a global level. We examined five different human cell types and in each case found evidence for antisense transcripts in 2900 to 6400 human genes. The distribution of antisense transcripts was distinct from that of sense transcripts, was non-random across the genome, and differed among cell types.Type: ApplicationFiled: December 2, 2009Publication date: January 12, 2012Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Bert Vogelstein, Kenneth W. Kinzler, Yiping He, Victor Velculescu, Nickolas Papadopoulos
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Publication number: 20110319477Abstract: Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the PI3K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the PI3K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.Type: ApplicationFiled: August 16, 2011Publication date: December 29, 2011Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Yardena SAMUELS, Victor VELCULESCU, Kenneth W. KINZLER, Bert VOGELSTEIN
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Patent number: 8039210Abstract: Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14) affecting 26% of colorectal cancers and a smaller fraction of lung, breast and gastric cancers. Fifteen mutations were nonsense, frameshift or splice site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRP) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the tyrosine phosphatase genes are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.Type: GrantFiled: May 16, 2005Date of Patent: October 18, 2011Assignee: The Johns Hopkins UniversityInventors: Zhenghe Wang, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
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Patent number: 8026053Abstract: Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the P13K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the P13K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.Type: GrantFiled: February 18, 2005Date of Patent: September 27, 2011Assignee: The Johns Hopkins UniversityInventors: Yardena Samuels, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
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Publication number: 20110229479Abstract: We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.Type: ApplicationFiled: September 3, 2009Publication date: September 22, 2011Applicants: THE JOHNS HOPKINS UNIVERSITY, DUKE UNIVERSITYInventors: Bert Vogelstein, Kenneth W. Kinzler, D. Williams Parsons, Xiaosong Zhang, Jimmy Cheng-Ho Lin, Rebecca J. Leary, Philipp Angenendt, Nickolas Papadopoulos, Victor Velculescu, Giovanni Parmigiani, Rachel Karchin, Sian Jones, Hai Yan, Darell Bigner, Chien-Tsun Kuan
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Publication number: 20110059434Abstract: Given the important role of protein kinases in pathways affecting cellular growth and invasion, we have analyzed 340 serine/threonine kinases for genetic mutations in colorectal cancers. Mutations in eight genes were identified, including three members of the phosphatidylinositol-3-kinase (PI3K) pathway; the alterations in the latter genes each occurred in different tumors and did not overlap with mutations in PIK3CA or other non-serine-threonine kinase (STK) members of the PI3K pathway, suggesting that mutations in any of these genes had equivalent tumorigenic effects. These data demonstrate that the PI3K pathway is a major target for mutational activation in colorectal cancers and provide new opportunities for therapeutic intervention.Type: ApplicationFiled: May 23, 2006Publication date: March 10, 2011Inventors: Donald William Parsons, Tian-li Wang, Yardena Samuels, Alberto Bardelli, Christopher Lengauer, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
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Publication number: 20100184100Abstract: Protein kinases are important signaling molecules involved in tumorigenesis. Mutational analysis of the human tyrosine kinase gene family (98 genes) identified somatic alterations in ?20% of colorectal cancers, with the majority of mutations occurring in NTRK3, FES, GUCY2F and a previously uncharacterized tyrosine kinase gene called MCCK/MLK4. Most alterations were in conserved residues affecting key regions of the kinase domain. These data represent a paradigm for the unbiased analysis of signal transducing genes in cancer and provide useful targets for therapeutic intervention.Type: ApplicationFiled: February 15, 2010Publication date: July 22, 2010Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Alberto Bardelli, Will Parsons, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
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Publication number: 20100137413Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. The public miRNA database contains 321 human miRNA sequences, 234 of which have been experimentally verified. To explore the possibility that additional miRNAs are present in the human genome, we have developed an experimental approach called miRNA serial analysis of gene expression (miRAGE) and used it to perform the largest experimental analysis of human miRNAs to date. Sequence analysis of 273,966 small RNA tags from human colorectal cells allowed us to identify 200 known mature miRNAs, 133 novel miRNA candidates, and 112 previously uncharacterized miRNA* forms. To aid in the evaluation of candidate miRNAs, we disrupted the Dicer locus in three human colorectal cancer cell lines and examined known and novel miRNAs in these cells. The miRNAs are useful to diagnose and treat cancers.Type: ApplicationFiled: February 16, 2007Publication date: June 3, 2010Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Jordan Cummins, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
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Patent number: 7704687Abstract: Alterations in the genetic content of a cell underlie many human diseases, including cancers. A method called Digital Karyotyping provides quantitative analysis of DNA copy number at high resolution. This approach involves the isolation and enumeration of short sequence tags from specific genomic loci. Analysis of human cancer cells using this method identified gross chromosomal changes as well as amplifications and deletions, including regions not previously known to be altered. Foreign DNA sequences not present in the normal human genome could also be readily identified. Digital Karyotyping provides a broadly applicable means for systematic detection of DNA copy number changes on a genomic scale.Type: GrantFiled: November 13, 2003Date of Patent: April 27, 2010Assignee: The Johns Hopkins UniversityInventors: Tian-Li Wang, Victor Velculescu, Kenneth Kinzler, Bert Vogelstein
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Publication number: 20090208505Abstract: Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the P13K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the P13K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.Type: ApplicationFiled: February 18, 2005Publication date: August 20, 2009Applicant: The Johns Hopkins UniversityInventors: Yardena Samuels, Victor Velculescu, Kenneth Kinzler, Bert Vogelstein
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Publication number: 20090123928Abstract: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalogue the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene “mountains” and a much larger number of gene “hills” that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.Type: ApplicationFiled: October 8, 2008Publication date: May 14, 2009Applicant: The Johns Hopkins UniversityInventors: Laura D. Wood, Williams D. Parsons, Sian Jones, Jimmy Lin, Tobias Sjoblom, Thomas Barber, Giovanni Parmigiani, Victor Velculescu, Kenneth W. Kinzler, Bert Vogelstein
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Publication number: 20080039417Abstract: Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14) affecting 26% of colorectal cancers and a smaller fraction of lung, breast and gastric cancers. Fifteen mutations were nonsense, frameshift or splice site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRP) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the tyrosine phosphatase genes are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.Type: ApplicationFiled: May 16, 2005Publication date: February 14, 2008Applicant: The Johns Hopkins UniversityInventors: Zhenghe Wang, Victor Velculescu, Bert Vogelstein
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Publication number: 20070037150Abstract: Protein kinases are important signaling molecules involved in tumorigenesis. Mutational analysis of the human tyrosine kinase gene family (98 genes) identified somatic alterations in ?20% of colorectal cancers, with the majority of mutations occurring in NTRK3, FES, GUCY2F and a previously uncharacterized tyrosine kinase gene called MCCK/MLK4. Most alterations were in conserved residues affecting key regions of the kinase domain. These data represent a paradigm for the unbiased analysis of signal transducing genes in cancer and provide useful targets for therapeutic intervention.Type: ApplicationFiled: February 18, 2004Publication date: February 15, 2007Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Alberto Bardelli, Will Parsons, Victor Velculescu, Kenneth Kinzler, Bert Vogelstein
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Publication number: 20070031851Abstract: Yeast genes which are differentially expressed during the cell cycle are described. They can be used to study, affect, and monitor the cell cycle of a eukaryotic cell. They can be used to obtain human homologs involved in cell cycle regulation. They can be used to identify antifungal agents and other classes of drugs. They can be formed into arrays on solid supports for interrogation of a cell's transcriptome under various conditions.Type: ApplicationFiled: August 11, 2004Publication date: February 8, 2007Applicant: The Johns Hopkins UniversityInventors: Victor Velculescu, Bert Vogelstein, Kenneth Kinzler
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Publication number: 20050202465Abstract: Thymidylate synthase (TYMS) gene amplification was observed in 23% of 31 5-FU resistant liver metastases, while no amplification was observed in metastases of patients that had not been treated with 5-FU. Patients with metastases containing TYMS amplification had a substantially shorter median survival (329 days) than those without amplification (1021 days, p<0.01). Genetic amplification of TYMS has important implications for the management of colorectal cancer patients with recurrent disease.Type: ApplicationFiled: November 24, 2004Publication date: September 15, 2005Applicant: The Johns Hopkins UniversityInventors: Tian-Li Wang, Luis Diaz, Christoph Lengauer, Victor Velculescu, Kenneth Kinzler, Bert Vogelstein