Clinical significance of large rearrangements in BRCA1 and BRCA2.
Clinical significance of large rearrangements in BRCA1 and BRCA2.
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DOI：
10.1002/cncr.27556
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发表时间：
2012-11-01
期刊：
影响因子：
6.2
通讯作者：
Roa, Benjamin B.
中科院分区：
文献类型：
--
作者：
Judkins, Thaddeus;Rosenthal, Eric;Arnell, Christopher;Burbidge, Lynn Anne;Geary, Wade;Barrus, Toby;Schoenberger, Jeremy;Trost, Jeffrey;Wenstrup, Richard J.;Roa, Benjamin B.
关键词：
背景技术背景：目前对BRCA 1（乳腺癌1，早发）和BRCA 2（乳腺癌2，早发）基因中大重排（LR）突变对遗传性乳腺癌和卵巢癌的贡献的估计是基于对相对同质患者人群的有限研究。在48，456例具有不同临床病史和血统的患者中调查了BRCA 1/2 LR的患病率，这些患者因怀疑遗传性乳腺癌和卵巢癌而进行临床分子检测。方法：使用定量多重聚合酶链反应试验对BRCA 1/2和LR检测的缺失和重复进行桑格测序分析。分析了2007年7月至2011年4月期间来自不同风险和种族群体的患者的患病率数据。如果患者的临床病史预测高先验概率，则将患者指定为“高风险”，其中LR测试与测序结合自动进行。“择期”患者不符合高风险标准，但按照转诊医疗服务提供者的要求进行LR检测。结果：高风险患者的总体BRCA 1/2突变患病率为23.8%，而择期组为8.2%。高风险患者的突变谱为90.1%测序突变与9.9% LR，对于择期患者，94.1%测序与5.9% LR。这种差异可能反映了高危患者携带BRCA 1突变的偏倚，与BRCA 2相比，BRCA 1具有更高的LR突变率和频率。不同家系患者的LR患病率和类型存在显著差异。LR突变在拉丁美洲/加勒比患者中明显更常见。结论：结合全基因测序的全面LR检测是临床BRCA 1/2分析的适当策略。
BACKGROUND: Current estimates of the contribution of large rearrangement (LR) mutations in the BRCA1 (breast cancer 1, early onset) and BRCA2 (breast cancer 2, early onset) genes responsible for hereditary breast and ovarian cancer are based on limited studies of relatively homogeneous patient populations. The prevalence of BRCA1/2 LRs was investigated in 48,456 patients with diverse clinical histories and ancestries, referred for clinical molecular testing for suspicion of hereditary breast and ovarian cancer. METHODS: Sanger sequencing analysis was performed for BRCA1/2 and LR testing for deletions and duplications using a quantitative multiplex polymerase chain reaction assay. Prevalence data were analyzed for patients from different risk and ethnic groups between July 2007 and April 2011. Patients were designated as “high-risk” if their clinical history predicted a high prior probability, wherein LR testing was performed automatically in conjunction with sequencing. “Elective” patients did not meet the high-risk criteria, but underwent LR testing as ordered by the referring health care provider. RESULTS: Overall BRCA1/2 mutation prevalence among high-risk patients was 23.8% versus 8.2% for the elective group. The mutation profile for high-risk patients was 90.1% sequencing mutations versus 9.9% LRs, and for elective patients, 94.1% sequencing versus 5.9% LRs. This difference may reflect the bias in high-risk patients to carry mutations in BRCA1, which has a higher penetrance and frequency of LRs compared with BRCA2. There were significant differences in the prevalence and types of LRs in patients of different ancestries. LR mutations were significantly more common in Latin American/Caribbean patients. CONCLUSIONS: Comprehensive LR testing in conjunction with full gene sequencing is an appropriate strategy for clinical BRCA1/2 analysis.
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影响因子：
3.7
作者：
Hendrickson, BC;Judkins, T;Scholl, T
通讯作者：
Scholl, T
影响因子：
120.7
作者：
Walsh, T;Casadei, S;King, MC
通讯作者：
King, MC
影响因子：
2.1
作者：
Ewald IP;Ribeiro PL;Palmero EI;Cossio SL;Giugliani R;Ashton-Prolla P
通讯作者：
Ashton-Prolla P
影响因子：
12.3
作者：
Brownstein Z;Friedman LM;Shahin H;Oron-Karni V;Kol N;Abu Rayyan A;Parzefall T;Lev D;Shalev S;Frydman M;Davidov B;Shohat M;Rahile M;Lieberman S;Levy-Lahad E;Lee MK;Shomron N;King MC;Walsh T;Kanaan M;Avraham KB
通讯作者：
Avraham KB
DOI：
10.1073/pnas.1115052108
发表时间：
2011-11-01
影响因子：
11.1
作者：
Walsh, Tom;Casadei, Silvia;Swisher, Elizabeth M.
通讯作者：
Swisher, Elizabeth M.