PALB2 mutations 1592delT and 229delT are not present in Korean breast cancer patients negative for BRCA1 and BRCA2 mutations

Kim, Jin Ho; Choi, Doo Ho; Cho, Dae Yeon; Son, Byung Ho; Haffty, Bruce G.

doi:10.1007/s10549-010-0806-2

Cited by 10 publications

(7 citation statements)

References 27 publications

(47 reference statements)

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“…A total of 4 previous studies have arisen from Asia. One study by Cao et al (16) from China revealed 3 cases out of 360 (0.8%) with the deleterious mutations, although there were none from Korea (300 cases) or from Malaysia (122 cases) (17,18). The previous study by the present authors on Japanese patients (n=155) revealed that none of them had the deleterious mutation (19).…”

Section: Discussionmentioning

confidence: 43%

PALB2 mutation in a woman with bilateral breast cancer: A case report

Nakagomi

Hirotsu

Okimoto

et al. 2017

Molecular and Clinical Oncology

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Abstract. Partner and localizer of breast cancer 2 (PALB2) was identified as a moderate-risk gene of breast and pancreas cancer. The present authors previously reported that no PALB2 germline mutations with a deleterious frameshift or stop codons were identified in 155 Japanese patients with breast and/or ovarian cancer who were estimated to be at risk of hereditary cancer, according to the National Comprehensive Cancer Network (NCCN) criteria. In the present study, one patient with a deleterious mutation of PALB2 (c. 2834+2 T>C) has been identified from a study of an additional 128 cases. Therefore, the prevalence of PALB2 among Japanese patients is now estimated to be 0.35% (1/283). The proband was a 63-year-old woman with bilateral breast cancer, although she had experienced no other cancers. The proband had two elder sisters, the eldest of whom died from pancreatic cancer at 60 years of age. The proband's 40-year-old daughter was affected, but did not show any malignancies. There are only a few reports concerning PALB2 mutations in Japan. To the best of our knowledge, this is the first case study to reveal the significance of DNA-repair genes in the development of malignancies in Japanese patients with breast cancer. IntroductionThe significance of the breast cancer 1 (BRCA1) and BRCA2 mutations in familial breast and ovarian cancer has been well established (1,2). However, the mutations of these genes are estimated to cause, at most, 20-30% of cases of hereditary breast cancer (3). The present authors studied the BRCA1/2 mutations in 191 patients in a previous study, but the prevalence was shown to be unexpectedly low (4,5). In fact, it was only 7% among the analyzed patients who had a family history of breast cancers.Partner and localizer of BRCA2 (PALB2) was identified as a moderate-risk gene in breast and pancreas cancer (6). PALB2 is located on chromosome 16p12.2 containing 13 exons and 12 introns, and is involved in BRCA2-associated pathways (6). Recently, Antoniou et al (7) reported that PALB2 carriers have a high risk of developing breast cancer, and concluded that the cumulative risk of mutation carrier was 34% by the age of 70 in their prospective follow-up study on 154 families.The prevalence of the PALB2 mutation was reported to be 1.2-3.4% in European countries, whereas it is very rare in Asian countries (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). To the best of our knowledge, no study has been performed that has identified the PALB2 deleterious mutation in Japanese patients with breast cancer. From our first cohort data, no deleterious PALB2 mutations were identified in 155 patients with breast and/or ovarian cancer who were estimated to be at risk of hereditary cancer according to the National Comprehensive Cancer Network (NCCN) criteria (19). In the present case study, an additional 128 cases having breast and/or ovarian cancer were studied, and the case of a patient with bilateral breast cancer is presented who harbors the deleterious mutation in PALB2. Factoring in the first cohort of 155 c...

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Section: Discussionmentioning

confidence: 43%

PALB2 mutation in a woman with bilateral breast cancer: A case report

Nakagomi

Hirotsu

Okimoto

et al. 2017

Molecular and Clinical Oncology

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“…As a matter of fact in a Finnish serie of 113 familial breast cancer cases one truncating mutation (1529delT) was identified in 3 families (2.7%), in 18/1918 unselected breast cancer cases (0.9%), and 6/2501 controls (0.2%) [3]. This mutation has not been detected in other series [12,13] and may represent a Finnish founder. A French Canadian founder mutation 2323C/T (Q775X), has also been reported in 2/356 (0.5%) unselected cases [14].…”

Section: Introductionmentioning

confidence: 89%

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

Balia

Sensi

Lombardi³

et al. 2010

Familial Cancer

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Rare germline monoallelic mutations in PALB2 confer a relative risk of breast cancer of 2 to 4-times. To better define the role of PALB2 in breast cancer susceptibility in Italian breast or breast-ovarian cancer families we screened 95 index cases negative for BRCA1/BRCA2 germline mutations. The mutational analysis of the PALB2 gene in a index case of an high risk breast cancer family, has identified a frameshift mutation (c.1517delG) in the exon 4 that leads to the formation of a stop codon, 12 residues downstream of the mutation (Leu451X). The mutation was identified in a woman 52 year old with an infiltrating ductal breast carcinoma and in two of the three sisters without breast cancer. Our results confirmed that PALB2 could be a susceptibility gene for familial breast cancer also in Italian population.

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“…In addition to younger age at onset of breast cancer [ 8 ], there are several distinctive features of breast cancer in Korea [ 9 10 11 ]. Unlike the Ashkenazi-Jewish population, highly recurrent founder mutations have not been detected, while the BRCA2 c.7480c>T mutation has been suggested as a candidate founder mutation in Korea [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Unlike the Ashkenazi-Jewish population, highly recurrent founder mutations have not been detected, while the BRCA2 c.7480c>T mutation has been suggested as a candidate founder mutation in Korea [ 9 ]. Some moderate-penetrance breast cancer susceptibility alleles, such as PALB2 1592delT and 229delT and CHEK2 1100delC, are not present in Korean patients [ 10 11 ]. Although the Korean Hereditary Breast Cancer (KOHBRA) study estimated the nationwide prevalence of BRCA mutations among a high-risk group of patients with hereditary breast cancer [ 12 ], there has been no study using exome sequencing in familial breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Exome sequencing in a breast cancer family withoutBRCAmutation

et al. 2015

Self Cite

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PurposeWe performed exome sequencing in a breast cancer family without BRCA mutations.Materials and MethodsA family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members.ResultsWe identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined.ConclusionUsing exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.

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PALB2 mutations 1592delT and 229delT are not present in Korean breast cancer patients negative for BRCA1 and BRCA2 mutations

Cited by 10 publications

References 27 publications

PALB2 mutation in a woman with bilateral breast cancer: A case report

PALB2 mutation in a woman with bilateral breast cancer: A case report

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

Exome sequencing in a breast cancer family withoutBRCAmutation

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