Germline PALB2 mutation analysis in breast-pancreas cancer families

Stadler, Zsofia K.; Salo‐Mullen, Erin; Sabbaghian, Nelly; Simon, Jennifer; Zhang, Liying; Kurtz, Robert J.; Offit, Kenneth; Foulkes, William D.; Tischkowitz, Marc

doi:10.1136/jmg.2010.087379

Cited by 29 publications

(23 citation statements)

References 15 publications

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“…Our results are in line with the results of these previous reports in which no PALB2 mutations, 9,14 or low prevalence of PALB2 mutations, 2,4,[7][8]10 were found. It should be mentioned that the relatively small sample size could be a possible explanation for that no mutation carrier was identified in the current study.…”

Section: Discussionsupporting

confidence: 93%

“…2 Mutations in this gene may be associated with familial clustering of PC and BC. [1][2][3][4][5][6][7][8][9][10] Previous studies have shown that PALB2-mutation-positive familial BC (FBC) patients were significantly more likely to have a relative with PC, 5 and that nearly all PALB2-mutation positive familial PC (FPC) families were affected by at least one BC case. 4 Given these findings and the fact that the prevalence of gene mutations varies between different populations, we aimed to determine the prevalence of PALB2 mutations in Dutch cohorts of non-BRCA1/2 FPC patients and of non-BRCA1/2 FBC patients with a personal or family history of PC.…”

Section: Introductionmentioning

confidence: 99%

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Routine testing for PALB2 mutations in familial pancreatic cancer families and breast cancer families with pancreatic cancer is not indicated

et al. 2011

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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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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Routine testing for PALB2 mutations in familial pancreatic cancer families and breast cancer families with pancreatic cancer is not indicated

et al. 2011

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“…Recently, PALB2 germline mutations have been independently implicated in both breast cancer (BC) and PC susceptibility [12,13]. In patients with PALB2-associated PC, a concomitant personal or family history of BC has been repeatedly observed [14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in Italy

Ghiorzo

Pensotti

Fornarini³

et al. 2011

Familial Cancer

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Pancreatic adenocarcinoma (PC) is the third most common cancer associated with BRCA mutations. Most notice has been given to BRCA2, while the association between BRCA1 and PC is less widely reported. Recently, PALB2 has been implicated in both PC and breast cancer (BC) susceptibility. We selected 29 Italian PC patients from a case-control study of PC according to their personal and family history of both PC and breast/ovarian cancer (BC/OC) and tested them for presence of germline mutations in BRCA1, BRCA2 and PALB2. We identified no germline mutations or deletions in PALB2, but detected 7 BRCA mutations (4 in BRCA1 and 3 in BRCA2). These findings suggest that PALB2 does not play a major role in PC susceptibility in our population. As we found an almost equal frequency of germline mutations in BRCA1 and BRCA2, germline alterations in either of these genes may explain a subset of Italian families presenting both PC and BC/OC. Moreover, as we began the observation of these families from probands who are affected by PC, we provide here a direct assessment of the role of PALB2 and BRCA mutations in PC susceptibility.

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“…The frequencies of these cancers in the family histories of our cohort are described in Additional file 1: Table S5A and Additional file 1: Table S5B, respectively. Multiple studies have identified PALB2 mutations in familial pancreatic cancer probands, several of which were found to have family histories including cases of breast cancer [8,29-31]. It should be noted that these mutations occur at relatively low frequencies (0–4%), which depend on the population being studied [8,32].…”

Section: Resultsmentioning

confidence: 99%

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

Hartley

Cavallone

Sabbaghian

et al. 2014

Hered Cancer Clin Pract

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BackgroundPALB2 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.MethodsThe 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.ResultsWe 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.ConclusionsPALB2 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.

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Germline PALB2 mutation analysis in breast-pancreas cancer families

Abstract: Mutations within the PALB2 gene are rare events that do not account for a substantial proportion of cancer susceptibility in breast-pancreas cancer families. Routine screening of breast-pancreas cancer families for the presence of PALB2 mutations appears to be low yield.

Cited by 29 publications

References 15 publications

Routine testing for PALB2 mutations in familial pancreatic cancer families and breast cancer families with pancreatic cancer is not indicated

Routine testing for PALB2 mutations in familial pancreatic cancer families and breast cancer families with pancreatic cancer is not indicated

Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in Italy

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

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