FaCD Online Syndrome Fact Sheet

Last updated: 27 Apr 2010

Name: PALB2-associated Familial Breast and Pancreatic Cancer

Mode of Inheritance: AD / multifact

Genes

PALB2/FANCN, mapped to 16p12

Tumor features

breast cancer
breast cancer, ductal
breast cancer, lobular
pancreatic adenocarcinoma

Tumor features (possible)

angiosarcoma
prostate cancer

Comment

Bi-allelic PALB2 mutations are associated with Fanconi anemia and a high risk of childhood cancer (see: FANCN). Women with a single germline PALB2 mutation have an increased risk of breast cancer[1-3]. Ages at diagnosis ranging from 29 to 98 years have been reported. At least in some cases, these mutations appear have a high penetrance[3] and familial clustering can be observed. Lobular as well as ductal breast cancer types, most of them ER and PR receptor positive[3], have been reported, as well as a case of hemangiosarcoma[3]. The Finnish founder mutation 1592delT is associated with an aggressive breast tumor phenotype[4].

Recently, PALB2 has been identified as a rare cause of familial clustering of pancreatic cancer as well as breast and pancreatic cancer[5]. In a series of 254 pancreatic cancer patients, only one clearly pathogenic PALB2 germline mutation, a deletion, was detected[6]. This patient had been diagnosed with breast cancer at age 47 years as well as with pancreatic cancer at age 61 years; her mother had been diagnosed with pancreatic cancer at age 83 years. This series consisted of 114 sporadic cancer cases, 80 familial pancreatic cancer cases without breast/ovarian cancer, 21 patients with more than 1 case of pancreatic cancer and with breast/ovarian cancer in their family, and 39 patients with breast/ovarian cancer but no pancreatic cancer in their relatives. PALB2 gene was sequenced in a series of 81 European familial pancreatic cancer families[7]. Three truncating mutations were identified and each of these three families also had a history of breast cancer.

In summary, PALB2 germline mutations appear to be rare cause of familial pancreatic cancer and pancreatic/breast/ovarian cancer families. Clustering of prostate cancer has been reported in PALB2 families[1]. Also check Pancreatic Cancer, Familial Clustering of.

References

[1] Erkko H, Xia B, Nikkilä J, Schleutker J, Syrjäkoski K, Mannermaa A, Kallioniemi A, Pylkäs K, Karppinen SM, Rapakko K, Miron A, Sheng Q, Li G, Mattila H, Bell DW, Haber DA, Grip M, Reiman M, Jukkola-Vuorinen A, Mustonen A, Kere J, Aaltonen LA, Kosma VM, Kataja V, Soini Y, Drapkin RI, Livingston DM, Winqvist R. A recurrent mutation in PALB2 in Finnish cancer families. Nature 2007; 446(7133):316-9.
[2] Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D, , Easton DF, Stratton MR. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nature genetics 2007; 39(2):165-7.
[3] Tischkowitz M, Xia B, Sabbaghian N, Reis-Filho JS, Hamel N, Li G, van Beers EH, Li L, Khalil T, Quenneville LA, Omeroglu A, Poll A, Lepage P, Wong N, Nederlof PM, Ashworth A, Tonin PN, Narod SA, Livingston DM, Foulkes WD. Analysis of PALB2/FANCN-associated breast cancer families. Proceedings of the National Academy of Sciences of the United States of America 2007; 104(16):6788-93.
[4] Heikkinen T, Kärkkäinen H, Aaltonen K, Milne RL, Heikkilä P, Aittomäki K, Blomqvist C, Nevanlinna H. The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype.Clin Cancer Res.2009 May 1;15(9):3214-22
[5] Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009 Apr 10;324(5924):217.
[6] Tischkowitz MD, Sabbaghian N, Hamel N, Borgida A, Rosner C, Taherian N, Srivastava A, Holter S, Rothenmund H, Ghadirian P, Foulkes WD, Gallinger S. Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer. Gastroenterology. 2009 Sep;137(3):1183-6.
[7] Slater EP, Langer P, Niemczyk E, Strauch K, Butler J, Habbe N, Neoptolemos J, Greenhalf W, Bartsch DK. PALB2 mutations in European familial pancreatic cancer families. Clin Genet. 2010 Mar 18. [Epub ahead of print]