Search

Your search keyword '"Wani, Shivangi"' showing total 5 results
Start Over Author "Wani, Shivangi" Topic mutation
5 results on '"Wani, Shivangi"'

1. Genomic analyses identify molecular subtypes of pancreatic cancer.

Author

Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grützmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM, Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, and Grimmond SM

Subjects
Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Carcinoma, Pancreatic Ductal classification, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal immunology, Carcinoma, Pancreatic Ductal metabolism, Carcinoma, Pancreatic Ductal pathology, Cell Line, Tumor, DNA Methylation, DNA-Binding Proteins genetics, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Hepatocyte Nuclear Factor 3-beta genetics, Hepatocyte Nuclear Factor 3-gamma genetics, Histone Demethylases genetics, Homeobox Protein Nkx-2.2, Homeodomain Proteins genetics, Humans, Mice, Nuclear Proteins genetics, Pancreatic Neoplasms immunology, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Prognosis, Receptors, Cytoplasmic and Nuclear genetics, Survival Analysis, Trans-Activators genetics, Transcription Factors genetics, Transcription, Genetic, Transcriptome, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Proteins genetics, Zebrafish Proteins, Genes, Neoplasm genetics, Genome, Human genetics, Genomics, Mutation genetics, Pancreatic Neoplasms classification, Pancreatic Neoplasms genetics
Abstract

Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

Published
2016
Full Text
View/download PDF

2. Whole genomes redefine the mutational landscape of pancreatic cancer.

Author

Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, Quinn MC, Robertson AJ, Fadlullah MZ, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Wani S, Wilson PJ, Markham E, Cloonan N, Anderson MJ, Fink JL, Holmes O, Kazakoff SH, Leonard C, Newell F, Poudel B, Song S, Taylor D, Waddell N, Wood S, Xu Q, Wu J, Pinese M, Cowley MJ, Lee HC, Jones MD, Nagrial AM, Humphris J, Chantrill LA, Chin V, Steinmann AM, Mawson A, Humphrey ES, Colvin EK, Chou A, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Pettitt JA, Merrett ND, Toon C, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Graham JS, Niclou SP, Bjerkvig R, Grützmann R, Aust D, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Falconi M, Zamboni G, Tortora G, Tempero MA, Gill AJ, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Pearson JV, Biankin AV, and Grimmond SM

Subjects
Adenocarcinoma drug therapy, Adenocarcinoma genetics, Animals, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal genetics, DNA Repair genetics, Female, Genes, BRCA1, Genes, BRCA2, Genetic Markers genetics, Genomic Instability genetics, Genotype, Humans, Mice, Pancreatic Neoplasms classification, Pancreatic Neoplasms drug therapy, Platinum pharmacology, Point Mutation genetics, Poly(ADP-ribose) Polymerase Inhibitors, Xenograft Model Antitumor Assays, DNA Mutational Analysis, Genome, Human genetics, Genomics, Mutation genetics, Pancreatic Neoplasms genetics
Abstract

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

Published
2015
Full Text
View/download PDF

3. Whole genomes redefine the mutational landscape of pancreatic cancer

Author

Biankin, Andrew V, Johns, Amber L, Mawson, Amanda, Chang, David K, Scarlett, Christopher J, Brancato, Mary-Anne L, Rowe, Sarah J, Simpson, Skye H, Martyn-Smith, Mona, Thomas, Michelle T, Chantrill, Lorraine A, Chin, Venessa T, Chou, Angela, Cowley, Mark J, Humphris, Jeremy L, Jones, Marc D, Scott Mead, R, Nagrial, Adnan M, Pajic, Marina, Pettit, Jessica, Pinese, Mark, Rooman, Ilse, Wu, Jianmin, Tao, Jiang, DiPietro, Renee, Watson, Clare, Steinmann, Angela, Ching Lee, Hong, Wong, Rachel, Pinho, Andreia V, Giry-Laterriere, Marc, Daly, Roger J, Musgrove, Elizabeth A, Sutherland, Robert L, Grimmond, Sean M, Waddell, Nicola, Kassahn, Karin S, Miller, David K, Wilson, Peter J, Patch, Ann-Marie, Song, Sarah, Harliwong, Ivon, Idrisoglu, Senel, Nourse, Craig, Nourbakhsh, Ehsan, Manning, Suzanne, Wani, Shivangi, Gongora, Milena, Anderson, Matthew, Holmes, Oliver, Leonard, Conrad, Taylor, Darrin, Wood, Scott, Xu, Christina, Nones, Katia, Lynn Fink, J, Christ, Angelika, Bruxner, Tim, Cloonan, Nicole, Newell, Felicity, Pearson, John V, Bailey, Peter, Quinn, Michael, Nagaraj, Shivashankar, Kazakoff, Stephen, Waddell, Nick, Krisnan, Keerthana, Quek, Kelly, Wood, David, Fadlullah, Muhammad ZH, Samra, Jaswinder S, Gill, Anthony J, Pavlakis, Nick, Guminski, Alex, Toon, Christopher, Asghari, Ray, Merrett, Neil D, Pavey, Darren, Das, Amitabha, Cosman, Peter H, Ismail, Kasim, O’Connnor, Chelsie, Lam Duncan McLeod, Vincent W, Pleass, Henry C, Richardson, Arthur, James, Virginia, Kench, James G, Cooper, Caroline L, Joseph, David, Sandroussi, Charbel, Crawford, Michael, Gallagher, James, Texler, Michael, Forest, Cindy, Laycock, Andrew, Epari, Krishna P, Ballal, Mo, Fletcher, David R, Mukhedkar, Sanjay, and Spry, Nigel A

Subjects
Cancer, Human Genome, Pancreatic Cancer, Digestive Diseases, Genetics, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Adenocarcinoma, Animals, Carcinoma, Pancreatic Ductal, DNA Mutational Analysis, DNA Repair, Female, Genes, BRCA1, Genes, BRCA2, Genetic Markers, Genome, Human, Genomic Instability, Genomics, Genotype, Humans, Mice, Mutation, Pancreatic Neoplasms, Platinum, Point Mutation, Poly(ADP-ribose) Polymerase Inhibitors, Xenograft Model Antitumor Assays, Australian Pancreatic Cancer Genome Initiative, General Science & Technology
Abstract

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

Published
2015

4. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

Author

Biankin, Andrew, Waddell, Nicola, Kassahn, Karin, Gingras, Marie-Claude, Muthuswamy, Lakshmi, Johns, Amber, Miller, David, Wilson, Peter, Patch, Ann-Marie, Wu, Jianmin, Chang, David, Cowley, Mark, Gardiner, Brooke, Song, Sarah, Harliwong, Ivon, Idrisoglu, Senel, Nourse, Craig, Nourbakhsh, Ehsan, Manning, Suzanne, Wani, Shivangi, Gongora, Milena, Pajic, Marina, Scarlett, Christopher, Gill, Anthony, Pinho, Andreia, Rooman, Ilse, Anderson, Matthew, Holmes, Oliver, Leonard, Conrad, Taylor, Darrin, Wood, Scott, Xu, Qinying, Nones, Katia, Fink, J, Christ, Angelika, Bruxner, Tim, Cloonan, Nicole, Kolle, Gabriel, Newell, Felicity, Pinese, Mark, Mead, R, Humphris, Jeremy, Kaplan, Warren, Jones, Marc, Colvin, Emily, Nagrial, Adnan, Humphrey, Emily, Chou, Angela, Chin, Venessa, Chantrill, Lorraine, Mawson, Amanda, Samra, Jaswinder, Kench, James, Lovell, Jessica, Daly, Roger, Merrett, Neil, Toon, Christopher, Epari, Krishna, Nguyen, Nam, Barbour, Andrew, Zeps, Nikolajs, Kakkar, Nipun, Zhao, Fengmei, Wu, Yuan, Wang, Min, Muzny, Donna, Fisher, William, Brunicardi, F, Hodges, Sally, Reid, Jeffrey, Drummond, Jennifer, Chang, Kyle, Han, Yi, Lewis, Lora, Dinh, Huyen, Buhay, Christian, Beck, Timothy, Timms, Lee, Sam, Michelle, Begley, Kimberly, Brown, Andrew, Pai, Deepa, Panchal, Ami, Buchner, Nicholas, De Borja, Richard, Denroche, Robert, Yung, Christina, Serra, Stefano, Onetto, Nicole, Mukhopadhyay, Debabrata, Tsao, Ming-Sound, Shaw, Patricia, Petersen, Gloria, Gallinger, Steven, Hruban, Ralph, Maitra, Anirban, Iacobuzio-Donahue, Christine, Schulick, Richard, Wolfgang, Christopher, and Morgan, Richard

Subjects
Animals, Axons, Carcinoma, Pancreatic Ductal, Gene Dosage, Gene Expression Regulation, Neoplastic, Genome, Humans, Kaplan-Meier Estimate, Mice, Mutation, Pancreatic Neoplasms, Proteins, Signal Transduction
Abstract

Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

Published
2012

5. Whole genomes redefine the mutational landscape of pancreatic cancer

Author

Waddell, Nicola, Pajic, Marina, Patch, Ann-Marie, Chang, David K, Kassahn, Karin S, Bailey, Peter, Johns, Amber L, Miller, David, Nones, Katia, Quek, Kelly, Quinn, Michael CJ, Robertson, Alan J, Fadlullah, Muhammad ZH, Bruxner, Tim JC, Christ, Angelika N, Harliwong, Ivon, Idrisoglu, Senel, Manning, Suzanne, Nourse, Craig, Nourbakhsh, Ehsan, Wani, Shivangi, Wilson, Peter J, Markham, Emma, Cloonan, Nicole, Anderson, Matthew J, Fink, J Lynn, Holmes, Oliver, Kazakoff, Stephen H, Leonard, Conrad, Newell, Felicity, Poudel, Barsha, Song, Sarah, Taylor, Darrin, Waddell, Nick, Wood, Scott, Xu, Qinying, Wu, Jianmin, Pinese, Mark, Cowley, Mark J, Lee, Hong C, Jones, Marc D, Nagrial, Adnan M, Humphris, Jeremy, Chantrill, Lorraine A, Chin, Venessa, Steinmann, Angela M, Mawson, Amanda, Humphrey, Emily S, Colvin, Emily K, Chou, Angela, Scarlett, Christopher J, Pinho, Andreia V, Giry-Laterriere, Marc, Rooman, Ilse, Samra, Jaswinder S, Kench, James G, Pettitt, Jessica A, Merrett, Neil D, Toon, Christopher, Epari, Krishna, Nguyen, Nam Q, Barbour, Andrew, Zeps, Nikolajs, Jamieson, Nigel B, Graham, Janet S, Niclou, Simone P, Bjerkvig, Rolf, Grützmann, Robert, Aust, Daniela, Hruban, Ralph H, Maitra, Anirban, Iacobuzio-Donahue, Christine A, Wolfgang, Christopher L, Morgan, Richard A, Lawlor, Rita T, Corbo, Vincenzo, Bassi, Claudio, Falconi, Massimo, Zamboni, Giuseppe, Tortora, Giampaolo, Tempero, Margaret A, Australian Pancreatic Cancer Genome Initiative, Gill, Anthony J, Eshleman, James R, Pilarsky, Christian, Scarpa, Aldo, Musgrove, Elizabeth A, Pearson, John V, Biankin, Andrew V, Grimmond, Sean M, Waddell, Nicola, Pajic, Marina, Patch Ann, Marie, Chang David, K., Kassahn Karin, S., Bailey, Peter, Johns Amber, L., Miller, David, Nones, Katia, Quek, Kelly, Quinn Michael, C. J., Robertson Alan, J., Fadlullah Muhammad, Z. H., Bruxner Tim, J. C., Christ Angelika, N., Harliwong, Ivon, Idrisoglu, Senel, Manning, Suzanne, Nourse, Craig, Nourbakhsh, Ehsan, Wani, Shivangi, Wilson Peter, J., Markham, Emma, Cloonan, Nicole, Anderson Matthew, J., Fink J., Lynn, Holmes, Oliver, Kazakoff Stephen, H., Leonard, Conrad, Newell, Felicity, Poudel, Barsha, Song, Sarah, Taylor, Darrin, Waddell, Nick, Wood, Scott, Xu, Qinying, Wu, Jianmin, Pinese, Mark, Cowley Mark, J., Lee Hong, C., Jones Marc, D., Nagrial Adnan, M., Humphris, Jeremy, Chantrill Lorraine, A., Chin, Venessa, Steinmann Angela, M., Mawson, Amanda, Humphrey Emily, S., Colvin Emily, K., Chou, Angela, Scarlett Christopher, J., Pinho Andreia, V., Giry Laterriere, Marc, Rooman, Ilse, Samra Jaswinder, S., Kench James, G., Pettitt Jessica, A., Merrett Neil, D., Toon, Christopher, Epari, Krishna, Nguyen Nam, Q., Barbour, Andrew, Zeps, Nikolaj, Jamieson Nigel, B., Graham Janet, S., Niclou Simone, P., Bjerkvig, Rolf, Gruetzmann, Robert, Aust, Daniela, Hruban Ralph, H., Maitra, Anirban, Iacobuzio Donahue Christine, A., Wolfgang Christopher, L., Morgan Richard, A., Lawlor Rita, T., Corbo, Vincenzo, Bassi, Claudio, Falconi, Massimo, Zamboni, Giuseppe, Tortora, Giampaolo, Tempero Margaret, A., Gill Anthony, J., Eshleman James, R., Pilarsky, Christian, Scarpa, Aldo, Musgrove Elizabeth, A., Pearson John, V., Biankin Andrew, V., Grimmond Sean, M., Basic (bio-) Medical Sciences, and Laboratory for Medical and Molecular Oncology

Subjects
Genome instability, DNA Repair, Genes, BRCA2, DNA Mutational Analysis, Genes, BRCA1, pancreatic ductal adenocarcinomas (PDACs), Mice, CDKN2A, 2.1 Biological and endogenous factors, Copy-number variation, Aetiology, Cancer, Genetics, Multidisciplinary, Chromothripsis, Genome, Genomics, copy number variation (CNV), whole-genome sequencing, Pancreatic Ductal, Female, Carcinoma, Pancreatic Ductal, Human, Genetic Markers, Genotype, General Science & Technology, PALB2, Biology, Adenocarcinoma, Poly(ADP-ribose) Polymerase Inhibitors, Article, Genomic Instability, Pancreatic Cancer, Rare Diseases, Australian Pancreatic Cancer Genome Initiative, Pancreatic cancer, medicine, Animals, Humans, Point Mutation, Platinum, Settore MED/06 - ONCOLOGIA MEDICA, Genome, Human, Human Genome, Carcinoma, medicine.disease, BRCA1, Xenograft Model Antitumor Assays, BRCA2, Pancreatic Neoplasms, Genes, Mutation, Human genome, Digestive Diseases
Abstract

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results