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Pancreatic cancer and Palb2

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https://www.readbyqxmd.com/read/28726808/prevalence-of-germ-line-mutations-in-cancer-genes-among-pancreatic-cancer-patients-with-a-positive-family-history
#1
Kari G Chaffee, Ann L Oberg, Robert R McWilliams, Neil Majithia, Brian A Allen, John Kidd, Nanda Singh, Anne-Renee Hartman, Richard J Wenstrup, Gloria M Petersen
PurposePanel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germ-line mutations. However, small sample sizes or number of genes evaluated limit prevalence estimates of these mutations. We estimated prevalence of mutations in PDAC patients with positive family history.MethodsWe sequenced 25 cancer susceptibility genes in lymphocyte DNA from 302 PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreatic Research Registry. Kindreds containing at least two first-degree relatives with PDAC met criteria for familial pancreatic cancer (FPC), while the remaining were familial, but not FPC...
July 20, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28488580/germline-mutations-in-pancreatic-cancer-and-potential-new-therapeutic-options
#2
REVIEW
Rille Pihlak, Juan W Valle, Mairéad G McNamara
Due to short-lived treatment responses in unresectable disease, pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers. There is availability of new information about germline and sporadic mutations in the deoxyribonucleic acid (DNA) damage repair pathway in PDAC in recent decades and the expectation is that novel targeted therapies will thus be developed. A variety of germline mutations (BRCA2, BRCA1, PALB2, CDKN2A, ATM, TP53 and mismatch repair genes MLH1, MSH2, MSH6) have been reported in these patients with the highest prevalence being BRCA1/2...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413668/palb2-mutation-in-a-woman-with-bilateral-breast-cancer-a-case-report
#3
Hiroshi Nakagomi, Yosuke Hirotsu, Kenichiro Okimoto, Ikuko Sakamoto, Kenji Amemiya, Satoko Nakagomi, Takeo Kubota, Hitoshi Mochizuki, Masao Omata
Partner and localizer of breast cancer 2 (PALB2) was identified as a moderate-risk gene of breast and pancreas cancer. The present authors previously reported that no PALB2 germline mutations with a deleterious frameshift or stop codons were identified in 155 Japanese patients with breast and/or ovarian cancer who were estimated to be at risk of hereditary cancer, according to the National Comprehensive Cancer Network (NCCN) criteria. In the present study, one patient with a deleterious mutation of PALB2 (c...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27768182/association-of-distinct-mutational-signatures-with-correlates-of-increased-immune-activity-in-pancreatic-ductal-adenocarcinoma
#4
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
June 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/27757719/characterization-of-a-novel-germline-palb2-duplication-in-a-hereditary-breast-and-ovarian-cancer-family
#5
Ciyu Yang, Angela G Arnold, Magan Trottier, Yukio Sonoda, Nadeem R Abu-Rustum, Oliver Zivanovic, Mark E Robson, Zsofia K Stadler, Michael F Walsh, David M Hyman, Kenneth Offit, Liying Zhang
PURPOSE: Mutations in PALB2 have been associated with a predisposition to breast and pancreatic cancers. This study aims to characterize a novel PALB2 exon 13 duplication in a hereditary breast and ovarian cancer family. METHODS: The PALB2 exon 13 duplication in this family was evaluated using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT™) and confirmed by multiplex ligation-dependent probe amplification (MLPA)...
December 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27732944/germline-mutations-in-japanese-familial-pancreatic-cancer-patients
#6
Erina Takai, Shinichi Yachida, Kyoko Shimizu, Junji Furuse, Emi Kubo, Akihiro Ohmoto, Masami Suzuki, Ralph H Hruban, Takuji Okusaka, Chigusa Morizane, Toru Furukawa
Clinicopathologic and genetic features of familial pancreatic cancer (FPC) in Asian countries remain largely unknown. The main purpose of this study was to determine the prevalence of FPC and to define causative FPC-predisposition genes in a Japanese cohort with pancreatic ductal adenocarcinoma (PDAC).We reviewed 1,197 patients with a pathologically proven PDAC and found that 88 (7.3%) were FPC patients who had at least one first-degree relative with PDAC. There were no significant differences between the FPC cases and sporadic cases in terms of gender, age, tumor location, stage, family history of any cancer except PDAC, and personal history of smoking, other cancers, diabetes mellitus and chronic pancreatitis...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27488870/the-prevalence-of-founder-mutations-among-individuals-from-families-with-familial-pancreatic-cancer-syndrome
#7
Marcin R Lener, Aniruddh Kashyap, Wojciech Kluźniak, Cezary Cybulski, Agnieszka Soluch, Sandra Pietrzak, Tomasz Huzarski, Jacek Gronwald, Jan Lubiński
PURPOSE: Familial pancreatic cancer describes families with at least two first-degree relatives with pancreatic cancer that do not fulfil the criteria of other inherited tumor syndromes with increased risks of pancreatic cancer. Although much has been learned regarding the aggregation of pancreatic cancer in some families, the genetic basis for this familial aggregation is poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among individuals from families with diagnosed familial pancreatic cancer syndrome and assessed their possible association with the familial pancreatic cancer (FPC) risk in Poland...
April 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27197284/association-of-common-susceptibility-variants-of-pancreatic-cancer-in-higher-risk-patients-a-pacgene-study
#8
Erica J Childs, Kari G Chaffee, Steven Gallinger, Sapna Syngal, Ann G Schwartz, Michele L Cote, Melissa L Bondy, Ralph H Hruban, Stephen J Chanock, Robert N Hoover, Charles S Fuchs, David N Rider, Laufey T Amundadottir, Rachael Stolzenberg-Solomon, Brian M Wolpin, Harvey A Risch, Michael G Goggins, Gloria M Petersen, Alison P Klein
Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer...
July 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27114589/benefit-of-surveillance-for-pancreatic-cancer-in-high-risk-individuals-outcome-of-long-term-prospective-follow-up-studies-from-three-european-expert-centers
#9
MULTICENTER STUDY
Hans Vasen, Isaura Ibrahim, Carmen Guillen Ponce, Emily P Slater, Elvira Matthäi, Alfredo Carrato, Julie Earl, Kristin Robbers, Anneke M van Mil, Thomas Potjer, Bert A Bonsing, Wouter H de Vos Tot Nederveen Cappel, Wilma Bergman, Martin Wasser, Hans Morreau, Günter Klöppel, Christoph Schicker, Martin Steinkamp, Jens Figiel, Irene Esposito, Evelina Mocci, Enrique Vazquez-Sequeiros, Alfonso Sanjuanbenito, Maria Muñoz-Beltran, José Montans, Peter Langer, Volker Fendrich, Detlef K Bartsch
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis. PATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC...
June 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27106063/mutation-analysis-of-the-palb2-gene-in-unselected-pancreatic-cancer-patients-in-the-czech-republic
#10
M Borecka, P Zemankova, M Vocka, P Soucek, J Soukupova, P Kleiblova, J Sevcik, Z Kleibl, M Janatova
Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among common solid cancer diagnoses. It has been shown that up to 10% of PDAC cases have a familial component. Characterization of PDAC-susceptibility genes could reveal high-risk individuals and patients that may benefit from tailored therapy. Hereditary mutations in PALB2 (Partner and Localizer of BRCA2) gene has been shown to predispose, namely to PDAC and breast cancers; however, frequencies of mutations vary among distinct geographical populations...
May 2016: Cancer Genetics
https://www.readbyqxmd.com/read/27038244/do-founder-mutations-characteristic-of-some-cancer-sites-also-predispose-to-pancreatic-cancer
#11
Marcin R Lener, Rodney J Scott, Wojciech Kluźniak, Piotr Baszuk, Cezary Cybulski, Anna Wiechowska-Kozłowska, Tomasz Huzarski, Tomasz Byrski, Józef Kładny, Sandra Pietrzak, Agnieszka Soluch, Anna Jakubowska, Jan Lubiński
Understanding of the etiology and risk of pancreatic cancer (PaCa) is still poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among PaCa patients and assessed their possible association with the risk of disease in Poland. In the study 383 PaCa patients and 4,000 control subjects were genotyped for founder mutations in: BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2 + 1G > A, del5395, I157T), NBS1 (657del5) and PALB2 (509_510delGA, 172_175delTTGT)...
August 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/26691940/-palb2-as-another-candidate-gene-for-genetic-testing-in-patients-with-hereditary-breast-cancer-in-czech-republic
#12
M Janatová, M Borecká, J Soukupová, P Kleiblová, J Stříbrná, M Vočka, P Zemánková, A Panczak, K Veselá, P Souček, L Foretová, Z Kleibl
BACKGROUND: The PALB2 (FANCN) gene was identified as a component of endogenous BRCA2 complex that encodes a DNA repair protein participating along with BRCA1 and BRCA 2 proteins in DNA double-strand break repair. Hereditary PALB2 mutations are associated with an increased risk of breast and pancreatic cancers in heterozygotes. Breast cancer risk for PALB2 mutation carriers has recently been estimated at 33-58% depending on family history of breast cancer; pancreatic cancer risk in carriers of PALB2 mutations has not been precisely quantified, yet...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/26654799/pancreatic-cancer-diagnostics-and-treatment-current-state
#13
REVIEW
Zdeněk Krška, Jan Šváb, David Hoskovec, Jan Ulrych
Pancreatic ductal adenocarcinoma (PDAC) represents permanent and ever rising issue worldwide. Five-year survival does not exceed 3 to 6%, i.e. the worst result among solid tumours. The article evaluates the current state of PDAC diagnostics and treatment specifying also development and trends. Percentage of non-resectable tumours due to locally advanced or metastatic condition varies 60-80%, mostly over 80%. Survival with non-resectable PDAC is 4 to 8 months (median 3.5). In contrast R0 resection shows the survival 18-27 months...
2015: Prague Medical Report
https://www.readbyqxmd.com/read/26641009/inherited-mutations-in-cancer-susceptibility-genes-are-common-among-survivors-of-breast-cancer-who-develop-therapy-related-leukemia
#14
Jane E Churpek, Rafael Marquez, Barbara Neistadt, Kimberly Claussen, Ming K Lee, Matthew M Churpek, Dezheng Huo, Howard Weiner, Mekhala Bannerjee, Lucy A Godley, Michelle M Le Beau, Colin C Pritchard, Tom Walsh, Mary-Claire King, Olufunmilayo I Olopade, Richard A Larson
BACKGROUND: Risk factors for the development of therapy-related leukemia (TRL), an often lethal late complication of cytotoxic therapy, remain poorly understood and may differ for survivors of different malignancies. Survivors of breast cancer (BC) now account for the majority of TRL cases, making the study of TRL risk factors in this population a priority. METHODS: Subjects with TRL after cytotoxic therapy for a primary BC were identified from the TRL registry at The University of Chicago...
January 15, 2016: Cancer
https://www.readbyqxmd.com/read/26440929/identification-of-germline-genetic-mutations-in-patients-with-pancreatic-cancer
#15
Erin E Salo-Mullen, Eileen M O'Reilly, David P Kelsen, Asad M Ashraf, Maeve A Lowery, Kenneth H Yu, Diane L Reidy, Andrew S Epstein, Anne Lincoln, Amethyst Saldia, Lauren M Jacobs, Rohini Rau-Murthy, Liying Zhang, Robert C Kurtz, Leonard Saltz, Kenneth Offit, Mark E Robson, Zsofia K Stadler
BACKGROUND: Pancreatic adenocarcinoma (PAC) is part of several cancer predisposition syndromes; however, indications for genetic counseling/testing are not well-defined. In the current study, the authors sought to determine mutation prevalence and characteristics that are predictive of an inherited predisposition for PAC. METHODS: A total of 175 consecutive patients with PAC who underwent clinical genetics assessment at Memorial Sloan Kettering Cancer Center between 2011 and 2014 were identified...
December 15, 2015: Cancer
https://www.readbyqxmd.com/read/26411315/analysis-of-palb2-mutations-in-155-japanese-patients-with-breast-and-or-ovarian-cancer
#16
Hiroshi Nakagomi, Ikuko Sakamoto, Yosuke Hirotsu, Kenji Amemiya, Hitoshi Mochiduki, Masao Omata
BACKGROUND: PALB2 (Partner and Localizer of BRCA2) was identified as a moderate-risk gene in breast and pancreatic cancers. Recently, it was reported that PALB2 carriers have a high risk of developing breast cancer, with the cumulative risk of 34 % by the age of 70. PATIENTS AND METHODS: Peripheral blood samples from 155 patients at risk for hereditary breast and/or ovarian cancer were tested for BRCA1/2 and PALB2 by targeted sequencing using a next-generation sequencer...
April 2016: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/26171187/pathogenic-palb2-mutation-in-metastatic-pancreatic-adenocarcinoma-and-neuroendocrine-tumour-a-case-report
#17
David Chan, Stephen Clarke, Anthony J Gill, Lorraine Chantrill, Jas Samra, Bob T Li, Tristan Barnes, Kazi Nahar, Nick Pavlakis
Adenocarcinoma of the pancreas is an aggressive malignancy with poor prognosis. Pancreatic neuroendocrine tumours (PNET) comprise ~3% of primary pancreatic neoplasms and they are more heterogeneous in their histological character and outcome. This is the case report of a 73-year-old female patient with synchronously diagnosed pancreatic adenocarcinoma and PNET, which is likely associated with a pathogenic partner and localizer of breast cancer 2, early onset (PALB2) mutation. The potential pathogenic significance of PALB2 and its association with various malignancies were investigated and the potential role of PALB2 in conferring sensitivity to chemotherapeutic agents, such as mitomycin C and cisplatin, was discussed...
July 2015: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/26098869/common-variation-at-2p13-3-3q29-7p13-and-17q25-1-associated-with-susceptibility-to-pancreatic-cancer
#18
MULTICENTER STUDY
Erica J Childs, Evelina Mocci, Daniele Campa, Paige M Bracci, Steven Gallinger, Michael Goggins, Donghui Li, Rachel E Neale, Sara H Olson, Ghislaine Scelo, Laufey T Amundadottir, William R Bamlet, Maarten F Bijlsma, Amanda Blackford, Michael Borges, Paul Brennan, Hermann Brenner, H Bas Bueno-de-Mesquita, Federico Canzian, Gabriele Capurso, Giulia M Cavestro, Kari G Chaffee, Stephen J Chanock, Sean P Cleary, Michelle Cotterchio, Lenka Foretova, Charles Fuchs, Niccola Funel, Maria Gazouli, Manal Hassan, Joseph M Herman, Ivana Holcatova, Elizabeth A Holly, Robert N Hoover, Rayjean J Hung, Vladimir Janout, Timothy J Key, Juozas Kupcinskas, Robert C Kurtz, Stefano Landi, Lingeng Lu, Ewa Malecka-Panas, Andrea Mambrini, Beatrice Mohelnikova-Duchonova, John P Neoptolemos, Ann L Oberg, Irene Orlow, Claudio Pasquali, Raffaele Pezzilli, Cosmeri Rizzato, Amethyst Saldia, Aldo Scarpa, Rachael Z Stolzenberg-Solomon, Oliver Strobel, Francesca Tavano, Yogesh K Vashist, Pavel Vodicka, Brian M Wolpin, Herbert Yu, Gloria M Petersen, Harvey A Risch, Alison P Klein
Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia...
August 2015: Nature Genetics
https://www.readbyqxmd.com/read/25896973/precision-medicine-for-advanced-pancreas-cancer-the-individualized-molecular-pancreatic-cancer-therapy-impact-trial
#19
RANDOMIZED CONTROLLED TRIAL
Lorraine A Chantrill, Adnan M Nagrial, Clare Watson, Amber L Johns, Mona Martyn-Smith, Skye Simpson, Scott Mead, Marc D Jones, Jaswinder S Samra, Anthony J Gill, Nicole Watson, Venessa T Chin, Jeremy L Humphris, Angela Chou, Belinda Brown, Adrienne Morey, Marina Pajic, Sean M Grimmond, David K Chang, David Thomas, Lucille Sebastian, Katrin Sjoquist, Sonia Yip, Nick Pavlakis, Ray Asghari, Sandra Harvey, Peter Grimison, John Simes, Andrew V Biankin
PURPOSE: Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies...
May 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/25719666/whole-genomes-redefine-the-mutational-landscape-of-pancreatic-cancer
#20
Nicola Waddell, Marina Pajic, Ann-Marie Patch, David K Chang, Karin S Kassahn, Peter Bailey, Amber L Johns, David Miller, Katia Nones, Kelly Quek, Michael C J Quinn, Alan J Robertson, Muhammad Z H Fadlullah, Tim J C Bruxner, Angelika N Christ, Ivon Harliwong, Senel Idrisoglu, Suzanne Manning, Craig Nourse, Ehsan Nourbakhsh, Shivangi Wani, Peter J Wilson, Emma Markham, Nicole Cloonan, Matthew J Anderson, J Lynn Fink, Oliver Holmes, Stephen H Kazakoff, Conrad Leonard, Felicity Newell, Barsha Poudel, Sarah Song, Darrin Taylor, Nick Waddell, Scott Wood, Qinying Xu, Jianmin Wu, Mark Pinese, Mark J Cowley, Hong C Lee, Marc D Jones, Adnan M Nagrial, Jeremy Humphris, Lorraine A Chantrill, Venessa Chin, Angela M Steinmann, Amanda Mawson, Emily S Humphrey, Emily K Colvin, Angela Chou, Christopher J Scarlett, Andreia V Pinho, Marc Giry-Laterriere, Ilse Rooman, Jaswinder S Samra, James G Kench, Jessica A Pettitt, Neil D Merrett, Christopher Toon, Krishna Epari, Nam Q Nguyen, Andrew Barbour, Nikolajs Zeps, Nigel B Jamieson, Janet S Graham, Simone P Niclou, Rolf Bjerkvig, Robert Grützmann, Daniela Aust, Ralph H Hruban, Anirban Maitra, Christine A Iacobuzio-Donahue, Christopher L Wolfgang, Richard A Morgan, Rita T Lawlor, Vincenzo Corbo, Claudio Bassi, Massimo Falconi, Giuseppe Zamboni, Giampaolo Tortora, Margaret A Tempero, Anthony J Gill, James R Eshleman, Christian Pilarsky, Aldo Scarpa, Elizabeth A Musgrove, John V Pearson, Andrew V Biankin, Sean M Grimmond
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...
February 26, 2015: Nature
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