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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Hereditary Cancer in Clinical Practice 1/2014

Mutation analysis of PALB2 in BRCA1 and BRCA2-negative breast and/or ovarian cancer families from Eastern Ontario, Canada

Hereditary Cancer in Clinical Practice > Ausgabe 1/2014
Taila Hartley, Luca Cavallone, Nelly Sabbaghian, Rachel Silva-Smith, Nancy Hamel, Olga Aleynikova, Erika Smith, Valerie Hastings, Pedro Pinto, Marc Tischkowitz, Eva Tomiak, William D Foulkes
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1897-4287-12-19) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

All authors made substantial contributions to the acquisition and interpretation of data and critical revision of the manuscript. MT, ET and WDF made substantial contributions to the conception and design of the study. TH, RSS, ES, VH, NH and ET were involved in patient care/coordination of the study. TH, NH, ET, WDF wrote the manuscript. LC, NS, PP performed the molecular genetic studies. OA provided pathology expertise for the study. NH and LC performed the LOH studies on tumor tissue. All authors read and approved the final manuscript.



PALB2 has emerged as a breast cancer susceptibility gene. Mutations in PALB2 have been identified in almost all breast cancer populations studied to date, but the rarity of these mutations and lack of information regarding their penetrance makes genetic counseling for these families challenging. We studied BRCA1/2 -negative breast and/or ovarian cancer families to a) assess the contribution of PALB2 mutations in this series and b) identify clinical, pathological and family history characteristics that might make PALB2 screening more efficient.


The coding region of the PALB2 gene was analyzed in 175 probands with family histories of breast and/or ovarian cancer ascertained from a single Canadian institution in Eastern Ontario.


We identified 2 probands with PALB2 mutations that are known or strongly considered to be pathogenic and 3 probands with missense mutations that are possibly pathogenic. One of the identified truncating mutations [c.3113G > A (p.Gly1000_Trp1038del – major product)], has been previously described while the other four mutations [c.3507_3508delTC (p.H1170Ffs*19), c.1846G > C (p.D616H), c.3418 T > G (p.W1140G), c.3287A > G (p.N1096S)] have not been previously reported. Loss of heterozygosity was detected in two breast tumors from one c.3507_3508delTC mutation carrier but not in other available tumors from that family or in tumors from carriers of other mutations.


PALB2 mutation screening identifies a small, but significant number of mutations in BRCA1/2 -negative breast and/or ovarian cancer families. We show that mutations are more likely to be found in families with three or more breast cancers as well as other BRCA2-related cancers. In our cohort, both clearly pathogenic mutations were identified in premenopausal breast cancer cases (2/77, 2.6%). Testing should be preferentially offered to affected women from such families.
Additional file 1: Figure S1: Predicted effect of truncating mutations on PALB2 protein. Figure S2. Pedigrees of the PALB2 missense mutation-carrier families. Figure S3. The c.3507_3508delTC (p.H1170Ffs*19) variant is expressed in lymphoblastoid cells from the patient. Table S1. Ontario guidelines for molecular analysis of BRCA1 and BRCA2. Table S2. Breast Tumor Characteristics. Table S3. Primers. Table S4. Variants found (n = 176) 89 individuals had no variants and 86 had 1 or more variants. Table S5. Total patient population screened. (A) Number of Pancreatic Cancer Cases in Families. (B) Number of Melanoma Cancer Cases in Families. (C) Number of Ovarian Cancer Cases in Families. (DOCX 499 KB)
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