PALB2: a novel inactivating mutation in a Italian breast cancer family

Balia, Cristina; Sensi, Elisa; Lombardi, Grazia; Roncella, Manuela; Bevilacqua, Generoso; Caligo, Maria A.

doi:10.1007/s10689-010-9382-1

Cited by 31 publications

(23 citation statements)

References 19 publications

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“…These observations suggested that PALB2 mutations are preferentially associated with families with history of both breast and pancreatic cancer. However, by taking into consideration the pertinent uncertainty (i.e., exact 95% confidence Interval), in the present study the overall frequency of PALB2 mutations detected among breast cancer families with C1 case of pancreatic cancer appears to be comparable to the frequency detected in the overall group of BRCAX families (2.1%) and to those previously reported [1,[3][4][5][6]. Thus, if an excess of PALB2 mutations is present in families with occurrences of both breast and pancreatic cancer, this is likely to be modest and detectable only by larger surveys.…”

supporting

confidence: 79%

“…In the first report, PALB2 truncating mutations were identified in 10/923 (1.1%) English familial breast cancer cases [1]. Subsequent studies in Spanish, Chinese and Italian familial breast cancer found truncating mutations with frequencies ranging between 0.8 and 1.1% [3][4][5][6]. Also, PALB2 founder mutations were observed in 2.7% Finnish [7] and 0.6% Polish [8] familial breast cancer cases, and in 0.7% French-Canadian breast cancer cases with early onset disease [9].…”

mentioning

confidence: 99%

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PALB2 germline mutations in familial breast cancer cases with personal and family history of pancreatic cancer

Peterlongo

Catucci

Pasquini

et al. 2010

Breast Cancer Res Treat

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Keywords PAB2 Á Familial breast cancer Á Breast cancer risk Á Pancreatic cancer risk Á Truncating mutation Á CRC To the Editor PALB2 (partner and localizer of BRCA2) has been recently described as a breast cancer predisposing gene [1,2]. In the first report, PALB2 truncating mutations were identified in 10/923 (1.1%) English familial breast cancer cases [1]. Subsequent studies in Spanish, Chinese and Italian familial breast cancer found truncating mutations with frequencies ranging between 0.8 and 1.1% [3][4][5][6]. Also, PALB2 founder mutations were observed in 2.7% Finnish [7] and 0.6% Polish [8] familial breast cancer cases, and in 0.7% French-Canadian breast cancer cases with early onset disease [9].Recently, exomic sequencing revealed a germline truncating mutation of PALB2 in a familial pancreatic cancer case [10]. In the same study, the sequencing of PALB2 in 96 additional familial pancreatic cancer patients, ascertained in the US, identified truncating mutations in three cases. A subsequent larger survey analyzed 254 sporadic and familial pancreatic cancer cases ascertained in Toronto and Montreal, including nine individuals who were also diagnosed with breast cancer, one of which was found to carry a 6.7-kb deletion involving exons 12 and 13 [11]. Interestingly, of the five PALB2 mutated pancreatic cancer cases reported in the above studies, two also developed breast cancer, including one patient with three additional breast cancer cases in the family. Moreover, two of the three remaining cases had C 2 relatives affected with breast cancer. The last case belonged to a family negative for breast cancer, but the reported pedigree was small and included only one female individual [10] Paolo Peterlongo, Irene Catucci are contributed equally to this work.

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supporting

confidence: 79%

mentioning

confidence: 99%

PALB2 germline mutations in familial breast cancer cases with personal and family history of pancreatic cancer

Peterlongo

Catucci

Pasquini

et al. 2010

Breast Cancer Res Treat

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“…LOH was observed in both the left and right breast tumors from the mother carrying the c.3507_3508delTC (p.H1170Ffs*19) mutation, but none of the other tumors showed loss of the wild-type allele [Figures 1B and 2B, data not shown for the tumor from the proband with c.3418 T > G (p.W1140G)]. These results are consistent with previous observations that LOH is an inconsistent feature of PALB2 tumors, even among tumors carrying identical predisposing mutations [13,14,21,22]. …”

Section: Resultssupporting

confidence: 91%

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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“…Importantly, all of the mutations discovered in a Chinese population occurred in exons 4 of PALB2, suggesting a potential hotspot (25). The c.1285_1286delAinsTC (p.I429SfsX12) mutation is localized in exon 4, whereas other Italian studies reported the PALB2 mutations localized in exon 4 and 5 (26,27), as well as in exon 2 and 13 (8), suggesting no mutational hot spot in the PALB2 gene for the Italian population.…”

Section: Discussionmentioning

confidence: 84%

A novel PALB2 truncating mutation in an Italian family with male breast cancer

et al. 2014

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Abstract. Male breast cancer (MBC) is a rare disease, accounting for ~1% of all breast cancer cases worldwide. Although other genes are also involved, predisposing genetic factors to MBC include germline mutations in the BRCA genes (BRCA2). Among the other genes, partner and localizer of BRCA2 (PALB2) is considered a moderate-penetrance breast cancer susceptibility gene that may also play a role in MBC predisposition. Thus, the aim of the present study was to determine the PALB2 gene status in 8 MBC cases selected from a cohort of 181 hereditary breast and/or ovarian cancer probands. We performed PALB2 mutational analysis by direct sequencing of 13 exons and adjacent intronic regions. This study showed the presence of a PALB2 truncating mutation in 1/8 (12.5%) cases. This novel mutation was named c.1285_1286delAinsTC (p.I429SfsX12) and is localized in exon 4 of PALB2, in the region encoding for the ChAM motif which is important for the efficient association of PALB2 to chromatin and for recruitment of the BRCA complex to accumulate RAD51 at double-strand break sites. Our findings indicate that PALB2 could be added to the list of breast cancer susceptibility genes also in families with MBC cases.

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PALB2: a novel inactivating mutation in a Italian breast cancer family

Cited by 31 publications

References 19 publications

PALB2 germline mutations in familial breast cancer cases with personal and family history of pancreatic cancer

PALB2 germline mutations in familial breast cancer cases with personal and family history of pancreatic cancer

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

A novel PALB2 truncating mutation in an Italian family with male breast cancer

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