The Norwegian PMS2 founder mutation c.989-1G > T shows high penetrance of microsatellite instable cancers with normal immunohistochemistry.
The Norwegian PMS2 founder mutation c.989-1G > T shows high penetrance of microsatellite instable cancers with normal immunohistochemistry.
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DOI：
10.1186/1897-4287-12-12
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发表时间：
2014
影响因子：
1.7
通讯作者：
Sjursen W
中科院分区：
文献类型：
--
作者：
Grindedal EM;Aarset H;Bjørnevoll I;Røyset E;Mæhle L;Stormorken A;Heramb C;Medvik H;Møller P;Sjursen W
使用免疫组织化学（IHC）选择病例进行错配修复（MMR）基因检测，我们未能识别出具有有害PMS2突变c.989-1G >t的大型亲属。该研究的目的是检验免疫组化和微卫星不稳定性分析（MSI）识别突变携带者的敏感性，并估计其外显率和表达。所有突变的携带者和专性携带者都被鉴定出来。所有癌症诊断均得到证实。对可用肿瘤进行免疫组化和msi分析。通过Kaplan-Meier算法计算阿姆斯特丹和Bethesda标准中包含的msi -高肿瘤和msi -高和低肿瘤的外显率。突变与癌症共分离的概率为0.000004。确定了56个承运人或义务承运人。AMS1/AMS2/Bethesda标准中15/18（83.3%）肿瘤中PMS2染色正常。msi分析显示15/21（71.4%）肿瘤为高msi， 4/21（19.0%）肿瘤为低msi。70岁时，AMS1癌症（结直肠癌）的外显率为30.6%，AMS2癌症为42.8%，Bethesda癌症为47.2%，msi高、低癌症为55.6%，msi高癌症为52.2%。该突变符合5级致病性标准。免疫组化对检测由突变引起的肿瘤不敏感。70岁时显示MSI的癌症的外显率为56%。除结直肠癌外，女性最常见的表达是子宫内膜癌和乳腺癌，男性最常见的表达是胃癌和前列腺癌。
Using immunohistochemistry (IHC) to select cases for mismatch repair (MMR) genetic testing, we failed to identify a large kindred with the deleterious PMS2 mutation c.989-1G > T. The purpose of the study was to examine the sensitivity of IHC and microsatellite instability-analysis (MSI) to identify carriers of the mutation, and to estimate its penetrance and expressions. All carriers and obligate carriers of the mutation were identified. All cancer diagnoses were confirmed. IHC and MSI-analysis were performed on available tumours. Penetrances of cancers included in the Amsterdam and the Bethesda Criteria, for MSI-high tumours and MSI-high and low tumours were calculated by the Kaplan-Meier algorithm. Probability for co-segregation of the mutation and cancers by chance was 0.000004. Fifty-six carriers or obligate carriers were identified. There was normal staining for PMS2 in 15/18 (83.3%) of tumours included in the AMS1/AMS2/Bethesda criteria. MSI-analysis showed that 15/21 (71.4%) of tumours were MSI-high and 4/21 (19.0%) were MSI-low. Penetrance at 70 years was 30.6% for AMS1 cancers (colorectal cancers), 42.8% for AMS2 cancers, 47.2% for Bethesda cancers, 55.6% for MSI-high and MSI-low cancers and 52.2% for MSI-high cancers. The mutation met class 5 criteria for pathogenicity. IHC was insensitive in detecting tumours caused by the mutation. Penetrance of cancers that displayed MSI was 56% at 70 years. Besides colorectal cancers, the most frequent expressions were carcinoma of the endometrium and breast in females and stomach and prostate in males.
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影响因子：
1.9
作者：
Weissman, Scott M.;Burt, Randall;Senter, Leigha
通讯作者：
Senter, Leigha
影响因子：
4.8
作者：
Guerrette, S;Acharya, S;Fishel, R
通讯作者：
Fishel, R
影响因子：
11.5
作者：
Gill, S;Lindor, NM;Thibodeau, SN
通讯作者：
Thibodeau, SN
影响因子：
3.9
作者：
Moller, Pal;Clark, Neal;Maehle, Lovise
通讯作者：
Maehle, Lovise
影响因子：
24.5
作者：
Kastrinos F;Steyerberg EW;Balmaña J;Mercado R;Gallinger S;Haile R;Casey G;Hopper JL;LeMarchand L;Lindor NM;Newcomb PA;Thibodeau SN;Syngal S;Colon Cancer Family Registry
通讯作者：
Colon Cancer Family Registry