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Heterozygous mutati...
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Wark, LandonUniversity of Manitoba,Winnipeg, Canada
(författare)
Heterozygous mutations in the PALB2 hereditary breast cancer predisposition gene impact on the three-dimensional nuclear organization of patient-derived cell lines
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
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2013-01-23
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John Wiley & Sons,2013
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-87853
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-87853URI
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https://doi.org/10.1002/gcc.22045DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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PALB2/FANCN is a BRCA1- and BRCA2-interacting Fanconi Anemia (FA) protein crucial for key BRCA2 genome caretaker functions. Heterozygous germline mutations in PALB2 predispose to breast cancer and biallelic mutations cause FA. FA proteins play a critical role in the telomere maintenance pathway, with telomeric shortening observed in FA cells. Less is known about telomere maintenance in the heterozygous state. Here, we investigate the roles of PALB2 heterozygous mutations in genomic instability, an important carcinogenesis precursor. Patient-derived lymphoblastoid (LCL) and fibroblast (FCL) cell lines with monoallelic truncating PALB2 mutations were investigated using a combination of molecular imaging techniques including centromeric FISH, telomeric Q-FISH and spectral karyotyping (SKY). Mitomycin C and Cisplatin sensitivity was assayed via cellular metabolism of WST-1. The PALB2 c.229delT FCL showed increases in telomere counts associated with increased mean intensity compared with two wild-type FCLs generated from first-degree relatives (P =1.04E-10 and P =9.68E-15) and it showed evidence of chromosomal rearrangements. Significant differences in centromere distribution were observed in one of three PALB2 heterozygous FCLs analyzed when compared with PALB2 wild-type, BRCA1 and BRCA2 heterozygous FCLs. No significant consistently increased sensitivity to Mitomycin C or Cisplatin was observed in LCLs. Our results are suggestive of an altered centromere distribution profile and a telomere instability phenotype. Together, these may indicate critical nuclear organization defects associated with the predisposition to transformation and early stage development of PALB2-related cancers.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Novak, DavidUniversity of Manitoba,Winnipeg, Canada
(författare)
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Sabbaghian, NellyMcGill University, Montreal, QC, Canada
(författare)
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Amrein, LilianSegal Cancer Centre, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada
(författare)
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Jangamreddy, Jaganmohan ReddyLady Davis Institute, Jewish General Hospital, Montreal, QC, Canada,Marek Los(Swepub:liu)jagre79
(författare)
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Cheang, MaryUniversity of Manitoba,Winnipeg, Canada
(författare)
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Pouchet, CarlyMcGill University, Montreal, QC, Canada
(författare)
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Aloyz, RaquelMcGill University, Montreal, QC, Canada
(författare)
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Foulkes, William D.McGill University, Montreal, QC, Canada
(författare)
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Mai, SabineUniversity of Manitoba,Winnipeg, Canada
(författare)
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Tischkowitz, MarcMcGill University, Montreal, QC, Canada
(författare)
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University of Manitoba,Winnipeg, CanadaMcGill University, Montreal, QC, Canada
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Genes, Chromosomes and Cancer: John Wiley & Sons52:5, s. 480-4941045-22571098-2264
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Till lärosätets databas
- Av författaren/redakt...
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Wark, Landon
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Novak, David
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Sabbaghian, Nell ...
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Amrein, Lilian
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Jangamreddy, Jag ...
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Cheang, Mary
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visa fler...
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Pouchet, Carly
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Aloyz, Raquel
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Foulkes, William ...
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Mai, Sabine
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Tischkowitz, Mar ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
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Genes, Chromosom ...
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Linköpings universitet