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Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

BIANKIN, Andrew V ; WADDELL, Nicola ; CHANG, David K ; COWLEY, Mark J ; GARDINER, Brooke B ; SONG, Sarah ; HARLIWONG, Ivon ; IDRISOGLU, Senel ; NOURSE, Craig ; NOURBAKHSH, Ehsan ; MANNING, Suzanne ; WANI, Shivangi ; KASSAHN, Karin S ; GONGORA, Milena ; PAJIC, Marina ; SCARIETT, Christopher J ; GILL, Anthony J ; PINHO, Andreia V ; ROOMAN, Ilse ; ANDERSON, Matthew ; HOMES, Oliver ; LEONARD, Conrad ; TAYLOR, Darrin ; GINGRAS, Marie-Claude ; WOOD, Scott ; QINYING XU ; NONES, Katia ; FINK, J. Lynn ; CHRIST, Angelika ; BRUXNER, Tim ; CLOONAN, Nicole ; KOLLE, Gabriel ; NEWELL, Felicity ; PINESE, Mark ; MUTHUSWAMY, Lakshmi B ; MEAD, R. Scott ; HUMPHRIS, Jeremy L ; KAPLAN, Warren ; JONES, Marc D ; COLVIN, Emily K ; NAGRIAL, Adnan M ; HUMPHREY, Emily S ; CHOU, Angela ; CHIN, Venessa T ; CHANTRILL, Lorraine A ; JOHNS, Amber L ; MAWSON, Amanda ; SAMRA, Jaswinder S ; KENCH, James G ; LOVELL, Jessica A ; DALY, Roger J ; MERRETT, Neil D ; TOON, Christopher ; EPARI, Krishna ; NGUYEN, Nam Q ; BARBOUR, Andrew ; MILLER, David K ; WILSON, Peter J ; PATCH, Ann-Marie ; JIANMIN WU

Nature (London), 2012-11, Vol.491 (7424), p.399-405 [Periódico revisado por pares]

London: Nature Publishing Group

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Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
Autor: BIANKIN, Andrew V ; WADDELL, Nicola ; CHANG, David K ; COWLEY, Mark J ; GARDINER, Brooke B ; SONG, Sarah ; HARLIWONG, Ivon ; IDRISOGLU, Senel ; NOURSE, Craig ; NOURBAKHSH, Ehsan ; MANNING, Suzanne ; WANI, Shivangi ; KASSAHN, Karin S ; GONGORA, Milena ; PAJIC, Marina ; SCARIETT, Christopher J ; GILL, Anthony J ; PINHO, Andreia V ; ROOMAN, Ilse ; ANDERSON, Matthew ; HOMES, Oliver ; LEONARD, Conrad ; TAYLOR, Darrin ; GINGRAS, Marie-Claude ; WOOD, Scott ; QINYING XU ; NONES, Katia ; FINK, J. Lynn ; CHRIST, Angelika ; BRUXNER, Tim ; CLOONAN, Nicole ; KOLLE, Gabriel ; NEWELL, Felicity ; PINESE, Mark ; MUTHUSWAMY, Lakshmi B ; MEAD, R. Scott ; HUMPHRIS, Jeremy L ; KAPLAN, Warren ; JONES, Marc D ; COLVIN, Emily K ; NAGRIAL, Adnan M ; HUMPHREY, Emily S ; CHOU, Angela ; CHIN, Venessa T ; CHANTRILL, Lorraine A ; JOHNS, Amber L ; MAWSON, Amanda ; SAMRA, Jaswinder S ; KENCH, James G ; LOVELL, Jessica A ; DALY, Roger J ; MERRETT, Neil D ; TOON, Christopher ; EPARI, Krishna ; NGUYEN, Nam Q ; BARBOUR, Andrew ; MILLER, David K ; WILSON, Peter J ; PATCH, Ann-Marie ; JIANMIN WU
Assuntos: Animals ; Axons ; Axons - metabolism ; Biological and medical sciences ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - pathology ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Dosage ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Genome - genetics ; Health aspects ; Humans ; Kaplan-Meier Estimate ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Mice ; Mutation ; Pancreatic cancer ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Proteins - genetics ; Signal Transduction ; Tumors
É parte de: Nature (London), 2012-11, Vol.491 (7424), p.399-405
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Descrição: 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.
Editor: London: Nature Publishing Group
Idioma: Inglês

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Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

London: Nature Publishing Group

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