Abstract
PALB2-mutation carriers not only have an increased risk for breast cancer (BC) but also for pancreatic cancer (PC). Thus far, PALB2 mutations have been mainly found in PC patients from families affected by both PC and BC. As it is well known that the prevalence of gene mutations varies between different populations, we studied the prevalence of PALB2 mutations in a Dutch cohort of non-BRCA1/2 familial PC (FPC) families and in non-BRCA1/2 familial BC (FBC) families with at least one PC case. Mutation analysis included direct sequencing and multiplex ligation-dependent probe amplification (MLPA) and was performed in a total of 64 patients from 56 distinct families (28 FPC families, 28 FBC families). In total, 31 patients (48%) originated from FPC families; 24 were FPC patients (77%), 6 had a personal history of BC (19%) and 1 was a suspected carrier (3.2%). The remaining 33 patients (52%) were all female BC patients of whom 31 (94%) had a family history of PC and 2 (6.1%) had a personal history of PC. In none of these 64 patients a PALB2 mutation was found. Therefore, PALB2 does not have a major causal role in familial clustering of PC and BC in non-BRCA1/2 families in the Dutch population.
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References
Rahman N, Seal S, Thompson D et al: PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 2007; 39: 165–167.
Jones S, Hruban RH, Kamiyama M et al: Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 2009; 324: 217.
Erkko H, Xia B, Nikkila J et al: A recurrent mutation in PALB2 in Finnish cancer families. Nature 2007; 446: 316–319.
Tischkowitz MD, Sabbaghian N, Hamel N et al: Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer. Gastroenterology 2009; 137: 1183–1186.
Casadei S, Norquist BM, Walsh T et al: Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res 2011; 71: 2222–2229.
Hellebrand H, Sutter C, Honisch E et al: Germline mutations in the PALB2 gene are population specific and occur with low frequencies in familial breast cancer. Hum Mutat 2011; 32: E2176–E2188.
Hofstatter EW, Domchek SM, Miron A et al: PALB2 mutations in familial breast and pancreatic cancer. Fam Cancer 2011; 10: 225–231.
Peterlongo P, Catucci I, Pasquini G et al: PALB2 germline mutations in familial breast cancer cases with personal and family history of pancreatic cancer. Breast Cancer Res Treat 2011; 126: 825–828.
Stadler ZK, Salo-Mullen E, Sabbaghian N et al: Germline PALB2 mutation analysis in breast-pancreas cancer families. J Med Genet 2011; 48: 523–525.
Slater EP, Langer P, Niemczyk E et al: PALB2 mutations in European familial pancreatic cancer families. Clin Genet 2010; 78: 490–494.
Brand RE, Lerch MM, Rubinstein WS et al: Advances in counselling and surveillance of patients at risk for pancreatic cancer. Gut 2007; 56: 1460–1469.
Xia B, Dorsman JC, Ameziane N et al: Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat Genet 2007; 39: 159–161.
Ameziane N, van den Ouweland AM, Adank MA et al: Lack of large genomic deletions in BRIP1, PALB2, and FANCD2 genes in BRCA1/2 negative familial breast cancer. Breast Cancer Res Treat 2009; 118: 651–653.
Adank MA, van Mil SE, Gille JJ, Waisfisz Q, Meijers-Heijboer H : PALB2 analysis in BRCA2-like families. Breast Cancer Res Treat 2011; 127: 357–362.
Acknowledgements
On behalf of the Dutch Research Group of Pancreatic Cancer Surveillance in High-Risk Individuals (in alphabetical order): Amsterdam Medical Center: Cora M Aalfs, Marcel GW Dijkgraaf, Paul Fockens, Dirk J Gouma, Jeanin E van Hooft, C Yung Nio, Theo AM van Os, Ellen MA Smets. Erasmus Medical Center: Katharina Biermann, Marco J Bruno, Henny van Duijl, Casper HJ van Eijck, Femme Harinck, Nanda Krak, Jan-Werner Poley, Anja Wagner. The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital: Eveline MA Bleiker, Annemieke Cats, Irma Kluijt, Anja van Rens, Grace Sidharta, Senno Verhoef. University Medical Center Groningen: Hendrik M van Dullemen, Rolf H Sijmons.
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Harinck, F., Kluijt, I., van Mil, S. et al. Routine testing for PALB2 mutations in familial pancreatic cancer families and breast cancer families with pancreatic cancer is not indicated. Eur J Hum Genet 20, 577–579 (2012). https://doi.org/10.1038/ejhg.2011.226
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DOI: https://doi.org/10.1038/ejhg.2011.226
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