Journal ArticleDOI
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer
Sarah Reid,Detlev Schindler,Helmut Hanenberg,Helmut Hanenberg,Karen Barker,Sandra Hanks,Reinhard Kalb,Kornelia Neveling,Patrick Kelly,Sheila Seal,Marcel Freund,Melanie Wurm,Sat Dev Batish,Sat Dev Batish,Francis P. Lach,Sevgi Yetgin,Heidemarie Neitzel,Hany Ariffin,Marc Tischkowitz,Marc Tischkowitz,Christopher G. Mathew,Arleen D. Auerbach,Nazneen Rahman +22 more
TLDR
It is demonstrated that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to bIALlelic BRCA2 mutations, confer a high risk of childhood cancer.Abstract:
PALB2 was recently identified as a nuclear binding partner of BRCA2. Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies. We identified pathogenic mutations in PALB2 (also known as FANCN) in seven families affected with Fanconi anemia and cancer in early childhood, demonstrating that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of childhood cancer.read more
Citations
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Journal ArticleDOI
Mechanism of eukaryotic homologous recombination.
TL;DR: HR accessory factors that facilitate other stages of the Rad51- and Dmc1-catalyzed homologous DNA pairing and strand exchange reaction have also been identified.
Journal ArticleDOI
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene
Nazneen Rahman,Sheila Seal,Deborah J. Thompson,Patrick Kelly,Anthony Renwick,Anna Elliott,Sarah Reid,Katarina Spanova,Rita Barfoot,Tasnim Chagtai,Hiran Jayatilake,Lesley McGuffog,Sandra Hanks,D. Gareth Evans,Diana Eccles,Douglas F. Easton,Michael R. Stratton +16 more
TL;DR: The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia–DNA repair pathway and breast cancer predisposition.
Journal ArticleDOI
Homologous recombination in DNA repair and DNA damage tolerance
Xuan Li,Wolf Dietrich Heyer +1 more
TL;DR: Mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support related to DNA double-stranded breaks and interstrand crosslinks are reviewed.
Journal ArticleDOI
DNA interstrand crosslink repair and cancer.
Andrew J. Deans,Stephen C. West +1 more
TL;DR: Understanding how the FA pathway links nucleases, helicases and other DNA-processing enzymes should lead to more targeted uses of ICL-inducing agents in cancer treatment and could provide novel insights into drug resistance.
Journal ArticleDOI
Germline Mutations in Predisposition Genes in Pediatric Cancer
Jinghui Zhang,Michael Walsh,Gang Wu,Michael N. Edmonson,Tanja A. Gruber,John Easton,Dale J. Hedges,Xiaotu Ma,Xin Zhou,Donald Yergeau,Mark R. Wilkinson,Bhavin Vadodaria,Xiang Chen,Rose B. McGee,Stacy Hines-Dowell,Regina Nuccio,Emily Quinn,Sheila A. Shurtleff,Michael Rusch,Aman Patel,Jared Becksfort,Shuoguo Wang,Meaghann S. Weaver,Li Ding,Elaine R. Mardis,Richard K. Wilson,Amar Gajjar,David W. Ellison,Alberto S. Pappo,Ching-Hon Pui,Kim E. Nichols,James R. Downing +31 more
TL;DR: Germline mutations in cancer-predisposing genes were identified in 8.5% of the children and adolescents with cancer, and family history did not predict the presence of an underlying predisposition syndrome in most patients.
References
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Journal ArticleDOI
Cancer risks in BRCA2 mutation carriers
TL;DR: In addition to the large risks of breast and ovarian cancers, BRCA2 mutations may be associated with increased risks of several other cancers.
Journal ArticleDOI
Biallelic Inactivation of BRCA2 in Fanconi Anemia
Niall G. Howlett,Toshiyasu Taniguchi,Susan B. Olson,Barbara Cox,Quinten Waisfisz,Christine E. M. de Die-Smulders,Nicole Persky,Markus Grompe,Hans Joenje,Gerard Pals,Hideyuki Ikeda,Edward A. Fox,Alan D. D'Andrea +12 more
TL;DR: It is shown that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRC a2 proteins, which may result in cancer risks similar to those observed in families withBRCA1 or BRCa2 mutations.
Journal ArticleDOI
Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2
Bing Xia,Qing Sheng,Koji Nakanishi,Akihiro Ohashi,Jianmin Wu,Nicole Christ,Xinggang Liu,Maria Jasin,Fergus J. Couch,David M. Livingston +9 more
TL;DR: PALB2 licenses key cellular biochemical properties of BRCA2 and ensures its tumor suppression function, as well as enabling homologous recombination (HR)-based, error-free DNA double-strand break repair (DSBR) and intra-S phase DNA damage checkpoint control.
Journal ArticleDOI
A 20-year perspective on the International Fanconi Anemia Registry (IFAR)
David I. Kutler,Bhuvanesh Singh,Bhuvanesh Singh,Bhuvanesh Singh,Jaya M. Satagopan,Jaya M. Satagopan,Jaya M. Satagopan,Sat Dev Batish,Sat Dev Batish,Sat Dev Batish,Marianne Berwick,Marianne Berwick,Marianne Berwick,Philip F. Giampietro,Philip F. Giampietro,Philip F. Giampietro,Helmut Hanenberg,Helmut Hanenberg,Helmut Hanenberg,Arleen D. Auerbach +19 more
TL;DR: The results of this study of patients registered in the IFAR over a 20-year period provide information that will enable better prediction of outcome and aid clinicians with decisions regarding major therapeutic modalities.
Journal ArticleDOI
Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells
Fabrice Lejeune,Lynne E. Maquat +1 more
TL;DR: It is believed that mammalian cells routinely utilize NMD to achieve proper levels of gene expression, and the extraordinary frequency of alternative splicing together with data indicating that naturally occurring transcripts other than alternatively spliced mRNAs are likewise targeted for NMD are believed.