Hereditary prostate cancer as a feature of Lynch syndrome.
Hereditary prostate cancer as a feature of Lynch syndrome.
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DOI：
10.1007/s10689-010-9388-8
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发表时间：
2011-03
期刊：
影响因子：
2.2
通讯作者：
Cooney, Kathleen A.
中科院分区：
文献类型：
--
作者：
Bauer, Christina M.;Ray, Anna M.;Halstead-Nussloch, Bronwen A.;Dekker, Robert G.;Raymond, Victoria M.;Gruber, Stephen B.;Cooney, Kathleen A.
林奇综合征是一种常染色体显性遗传疾病，其特征是早发性结直肠癌 (CRC)，与胃肠道和生殖道癌症相关。 DNA 错配修复 (MMR) 基因的种系突变与林奇综合征癌症存在因果关系。我们调查了有结直肠癌病史的家族中前列腺癌 (PCa) 的发生情况，以评估前列腺癌作为林奇综合征谱系的一个特征。确定了至少包含 1 例 CRC 病例以及符合林奇综合征指南的家族谱系，并要求接受根治性前列腺切除术 (RP) 的参与者提供肿瘤。对选定的家庭进行了与 PCa 类型和侵袭性疾病临床特征的关联分析。对可用肿瘤进行微卫星不稳定性 (MSI) 分析，并通过免疫组织化学 (IHC) 染色与 MMR 基因表达缺失相关。 95 名个体被确定为接受 RP 的潜在林奇综合征家族成员，并收到来自 31 个家族的 35 个肿瘤进行 MSI 分析。来自两个具有已知 MMR 突变的不相关家族的两个肿瘤为高 MSI，来自第三个家族的另外一个病例为低 MSI。其余前列腺癌病例没有显示 MSI 证据。在具有林奇综合征癌症病史的遗传性前列腺癌家族中，前列腺癌的发病率并不能强烈提示存在 MMR 突变。然而，已知 MMR 突变携带者的前列腺肿瘤确实表现出 MSI 和基因表达缺失，这表明林奇综合征中可能由于 DNA 错配修复缺陷而出现 PCa。
Lynch Syndrome is an autosomal dominant condition characterized by early onset colorectal cancer (CRC) and is associated with cancers of the gastrointestinal and reproductive tracts. Germline mutations in DNA mismatch repair (MMR) genes have been causally associated with cancers of Lynch Syndrome. We investigated the occurrence of prostate cancer (PCa) in families with a history of colorectal cancer to assess prostate cancer as a feature of the Lynch Syndrome spectrum. Family pedigrees containing at least one CRC case as well as those meeting guidelines for Lynch Syndrome were identified and tumors were requested from participants who underwent radical prostatectomy (RP). Selected families were analyzed for association with type of PCa and clinical characteristics of aggressive disease. Microsatellite Instability (MSI) analysis was preformed on available tumors and correlated to loss of expression in MMR genes by immunohistochemical (IHC) staining. 95 individuals were identified as members of potential Lynch Syndrome families who underwent RP and 35 tumors from 31 families were received for MSI analysis. Two tumors from two unrelated families with known MMR mutations were MSI-high and one additional case from a third family was MSI-low. The remainder of the prostate cancer cases demonstrated no evidence of MSI. PCa incidence in families enriched for hereditary PCa with a history of Lynch Syndrome cancers is not strongly suggestive of the presence of an MMR mutation. However prostate tumors in known MMR mutation carriers did display MSI and loss of gene expression suggesting that PCa may arise in Lynch Syndrome due to defective DNA mismatch repair.
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影响因子：
3.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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Vasen H
影响因子：
29.4
作者：
Vasen, HFA;Watson, P;Lynch, HT
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Lynch, HT
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作者：
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通讯作者：
Gruber SB