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{"title"=>"Identification of BRCA1/2 Founder Mutations in Southern Chinese Breast Cancer Patients Using Gene Sequencing and High Resolution DNA Melting Analysis", "type"=>"journal", "authors"=>[{"first_name"=>"Ava", "last_name"=>"Kwong", "scopus_author_id"=>"8913654300"}, {"first_name"=>"Enders Kai On", "last_name"=>"Ng", "scopus_author_id"=>"21135553700"}, {"first_name"=>"Chris Lei Po", "last_name"=>"Wong", "scopus_author_id"=>"8987839600"}, {"first_name"=>"Fian Bic Fai", "last_name"=>"Law", "scopus_author_id"=>"35181537900"}, {"first_name"=>"Tommy", "last_name"=>"Au", "scopus_author_id"=>"24597501100"}, {"first_name"=>"Hong Nei", "last_name"=>"Wong", "scopus_author_id"=>"55355501900"}, {"first_name"=>"Allison W.", "last_name"=>"Kurian", "scopus_author_id"=>"56730290700"}, {"first_name"=>"Dee W.", "last_name"=>"West", "scopus_author_id"=>"7401998438"}, {"first_name"=>"James M.", "last_name"=>"Ford", "scopus_author_id"=>"7402915714"}, {"first_name"=>"Edmond Siu Kwan", "last_name"=>"Ma", "scopus_author_id"=>"55356328300"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"22970155", "doi"=>"10.1371/journal.pone.0043994", "sgr"=>"84866068268", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84866068268", "issn"=>"19326203", "pui"=>"365625459"}, "id"=>"7d6292fa-1824-3c3c-9ec6-e4ff94419e27", "abstract"=>"BACKGROUND: Ethnic variations in breast cancer epidemiology and genetics have necessitated investigation of the spectra of BRCA1 and BRCA2 mutations in different populations. Knowledge of BRCA mutations in Chinese populations is still largely unknown. We conducted a multi-center study to characterize the spectra of BRCA mutations in Chinese breast and ovarian cancer patients from Southern China.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: A total of 651 clinically high-risk breast and/or ovarian cancer patients were recruited from the Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2011. Comprehensive BRCA1 and BRCA2 mutation screening was performed using bi-directional sequencing of all coding exons of BRCA1 and BRCA2. Sequencing results were confirmed by in-house developed full high resolution DNA melting (HRM) analysis. Among the 451 probands analyzed, 69 (15.3%) deleterious BRCA mutations were identified, comprising 29 in BRCA1 and 40 in BRCA2. The four recurrent BRCA1 mutations (c.470_471delCT, c.3342_3345delAGAA, c.5406+1_5406+3delGTA and c.981_982delAT) accounted for 34.5% (10/29) of all BRCA1 mutations in this cohort. The four recurrent BRCA2 mutations (c.2808_2811delACAA, c.3109C>T, c.7436_7805del370 and c.9097_9098insA) accounted for 40% (16/40) of all BRCA2 mutations. Haplotype analysis was performed to confirm 1 BRCA1 and 3 BRCA2 mutations are putative founder mutations. Rapid HRM mutation screening for a panel of the founder mutations were developed and validated.\\n\\nCONCLUSION: In this study, our findings suggest that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Southern Chinese population. Knowing the spectrum and frequency of the founder mutations in this population will assist in the development of a cost-effective rapid screening assay, which in turn facilitates genetic counseling and testing for the purpose of cancer risk assessment.", "link"=>"http://www.mendeley.com/research/identification-brca12-founder-mutations-southern-chinese-breast-cancer-patients-using-gene-sequencin-1", "reader_count"=>38, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>4, "Other"=>3, "Student > Master"=>5, "Student > Bachelor"=>8}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>4, "Other"=>3, "Student > Master"=>5, "Student > Bachelor"=>8}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>24, "Medicine and Dentistry"=>3, "Social Sciences"=>1, "Immunology and Microbiology"=>1, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Pakistan"=>1, "China"=>1, "Germany"=>1}, "group_count"=>5}

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• http://doi.org/10.1002/ijc.32176
• http://doi.org/10.1002/ijc.28966
• http://doi.org/10.18632/oncotarget.23471
• http://doi.org/10.1002/ijc.30692
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• {"files"=>["https://ndownloader.figshare.com/files/305927", "https://ndownloader.figshare.com/files/305975", "https://ndownloader.figshare.com/files/306059", "https://ndownloader.figshare.com/files/306107", "https://ndownloader.figshare.com/files/306151"], "description"=>"<div><h3>Background</h3><p>Ethnic variations in breast cancer epidemiology and genetics have necessitated investigation of the spectra of <em>BRCA1</em> and <em>BRCA2</em> mutations in different populations. Knowledge of <em>BRCA</em> mutations in Chinese populations is still largely unknown. We conducted a multi-center study to characterize the spectra of <em>BRCA</em> mutations in Chinese breast and ovarian cancer patients from Southern China.</p> <h3>Methodology/Principal Findings</h3><p>A total of 651 clinically high-risk breast and/or ovarian cancer patients were recruited from the Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2011. Comprehensive <em>BRCA1</em> and <em>BRCA2</em> mutation screening was performed using bi-directional sequencing of all coding exons of <em>BRCA1</em> and <em>BRCA2</em>. Sequencing results were confirmed by in-house developed full high resolution DNA melting (HRM) analysis. Among the 451 probands analyzed, 69 (15.3%) deleterious <em>BRCA</em> mutations were identified, comprising 29 in <em>BRCA1</em> and 40 in <em>BRCA2</em>. The four recurrent <em>BRCA1</em> mutations (c.470_471delCT, c.3342_3345delAGAA, c.5406+1_5406+3delGTA and c.981_982delAT) accounted for 34.5% (10/29) of all <em>BRCA1</em> mutations in this cohort. The four recurrent <em>BRCA2</em> mutations (c.2808_2811delACAA, c.3109C>T, c.7436_7805del370 and c.9097_9098insA) accounted for 40% (16/40) of all <em>BRCA2</em> mutations. Haplotype analysis was performed to confirm 1 <em>BRCA1</em> and 3 <em>BRCA2</em> mutations are putative founder mutations. Rapid HRM mutation screening for a panel of the founder mutations were developed and validated.</p> <h3>Conclusion</h3><p>In this study, our findings suggest that <em>BRCA</em> mutations account for a substantial proportion of hereditary breast/ovarian cancer in Southern Chinese population. Knowing the spectrum and frequency of the founder mutations in this population will assist in the development of a cost-effective rapid screening assay, which in turn facilitates genetic counseling and testing for the purpose of cancer risk assessment.</p> </div>", "links"=>[], "tags"=>["mutations", "chinese", "cancer", "patients", "sequencing", "dna", "melting"], "article_id"=>120354, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Ava Kwong", "Enders Kai On Ng", "Chris Lei Po Wong", "Fian Bic Fai Law", "Tommy Au", "Hong Nei Wong", "Allison W. Kurian", "Dee W. West", "James M. Ford", "Edmond Siu Kwan Ma"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0043994.s001", "https://dx.doi.org/10.1371/journal.pone.0043994.s002", "https://dx.doi.org/10.1371/journal.pone.0043994.s003", "https://dx.doi.org/10.1371/journal.pone.0043994.s004", "https://dx.doi.org/10.1371/journal.pone.0043994.s005"], "stats"=>{"downloads"=>36, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Identification_of_BRCA1_2_Founder_Mutations_in_Southern_Chinese_Breast_Cancer_Patients_Using_Gene_Sequencing_and_High_Resolution_DNA_Melting_Analysis/120354", "title"=>"Identification of <em>BRCA1/2</em> Founder Mutations in Southern Chinese Breast Cancer Patients Using Gene Sequencing and High Resolution DNA Melting Analysis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-07 00:05:54"}
• {"files"=>["https://ndownloader.figshare.com/files/580110"], "description"=>"<p>The melting profile of a wild type (WT) control is chosen as a horizontal base line and the relative differences in the melting of other samples are plotted relative to this baseline. Each trace represents the amplicon from a different individual's DNA sample. Melt curves of the <i>BRCA2</i> founder mutations (green/red) were plotted against melt curve of the wild type (blue).</p>", "links"=>[], "tags"=>["mutations"], "article_id"=>250599, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Ava Kwong", "Enders Kai On Ng", "Chris Lei Po Wong", "Fian Bic Fai Law", "Tommy Au", "Hong Nei Wong", "Allison W. Kurian", "Dee W. West", "James M. Ford", "Edmond Siu Kwan Ma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043994.g002", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Difference_plot_showing_the_three_BRCA2_founder_mutations_relative_to_the_wild_type_controls_/250599", "title"=>"Difference plot showing the three <i>BRCA2</i> founder mutations relative to the wild type controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-07 00:09:59"}
• {"files"=>["https://ndownloader.figshare.com/files/579988"], "description"=>"<p>The melting profile of a wild type (WT) control is chosen as a horizontal base line and the relative differences in the melting of other samples are plotted relative to this baseline. Each trace represents the amplicon from a different individual's DNA sample. Melt curves of the <i>BRCA1</i> founder mutations (green/red) were plotted against melt curve of the wild type (blue).</p>", "links"=>[], "tags"=>["recurrent", "mutations"], "article_id"=>250473, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Ava Kwong", "Enders Kai On Ng", "Chris Lei Po Wong", "Fian Bic Fai Law", "Tommy Au", "Hong Nei Wong", "Allison W. Kurian", "Dee W. West", "James M. Ford", "Edmond Siu Kwan Ma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043994.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Difference_plot_showing_the_BRCA1_recurrent_or_founder_mutations_relative_to_the_wild_type_controls_/250473", "title"=>"Difference plot showing the <i>BRCA1</i> recurrent or founder mutations relative to the wild type controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-07 00:07:53"}
• {"files"=>["https://ndownloader.figshare.com/files/580261"], "description"=>"<p>\n <i>Abbreviations: F, Female; M, Male; GD, Guangdong; N/A, Not available; BC, Breast cancer; OC, Ovarian cancer;</i></p>", "links"=>[], "tags"=>["probands", "mutations", "mutation"], "article_id"=>250746, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Ava Kwong", "Enders Kai On Ng", "Chris Lei Po Wong", "Fian Bic Fai Law", "Tommy Au", "Hong Nei Wong", "Allison W. Kurian", "Dee W. West", "James M. Ford", "Edmond Siu Kwan Ma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043994.t003", "stats"=>{"downloads"=>4, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_all_probands_with_BRCA1_2_recurrent_founder_mutations_with_other_mutations_and_without_mutation_N_451_/250746", "title"=>"Characteristics of all probands with <i>BRCA1</i>/<i>2</i> recurrent/founder mutations, with other mutations and without mutation (N = 451).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-07 00:12:26"}
• {"files"=>["https://ndownloader.figshare.com/files/580344"], "description"=>"*<p>M13F: TGTAAAACGACGGCCAGT.</p>#<p>M13R: CAGGAAACAGCTATGACC.</p>", "links"=>[], "tags"=>["pcr", "primer", "sequences", "recurrent"], "article_id"=>250828, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Ava Kwong", "Enders Kai On Ng", "Chris Lei Po Wong", "Fian Bic Fai Law", "Tommy Au", "Hong Nei Wong", "Allison W. Kurian", "Dee W. West", "James M. Ford", "Edmond Siu Kwan Ma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043994.t004", "stats"=>{"downloads"=>9, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HRM_PCR_primer_sequences_for_the_BRCA_recurrent_or_founder_mutations_/250828", "title"=>"HRM PCR primer sequences for the <i>BRCA</i> recurrent or founder mutations.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-07 00:13:48"}
• {"files"=>["https://ndownloader.figshare.com/files/580293"], "description"=>"<p>Comparisons between HRM screening and sequencing of <i>BRCA1</i> and <i>BRCA2</i> genes.</p>", "links"=>[], "tags"=>["hrm", "sequencing"], "article_id"=>250781, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Ava Kwong", "Enders Kai On Ng", "Chris Lei Po Wong", "Fian Bic Fai Law", "Tommy Au", "Hong Nei Wong", "Allison W. Kurian", "Dee W. West", "James M. Ford", "Edmond Siu Kwan Ma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043994.t002", "stats"=>{"downloads"=>7, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparisons_between_HRM_screening_and_sequencing_of_BRCA1_and_BRCA2_genes_/250781", "title"=>"Comparisons between HRM screening and sequencing of <i>BRCA1</i> and <i>BRCA2</i> genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-07 00:13:01"}
• {"files"=>["https://ndownloader.figshare.com/files/580218"], "description"=>"<p>\n <b><i>Abbreviation</i></b><i>: SS, Splice-site mutation; NS, Nonsense mutation; FS, Frame-shift mutation; IFD, In-frame deletion mutation. Recurrent mutations are highlighted in bold.</i></p>", "links"=>[], "tags"=>["pathogenic", "mutations"], "article_id"=>250703, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Ava Kwong", "Enders Kai On Ng", "Chris Lei Po Wong", "Fian Bic Fai Law", "Tommy Au", "Hong Nei Wong", "Allison W. Kurian", "Dee W. West", "James M. Ford", "Edmond Siu Kwan Ma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0043994.t001", "stats"=>{"downloads"=>12, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spectrum_of_BRCA_pathogenic_mutations_identified_/250703", "title"=>"Spectrum of <i>BRCA</i> pathogenic mutations identified.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-07 00:11:43"}

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Relative Metric

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F1000Prime