Tumor testing to identify lynch syndrome in two Australian colorectal cancer cohorts.
Tumor testing to identify lynch syndrome in two Australian colorectal cancer cohorts.
复制标题
DOI：
10.1111/jgh.13468
复制
发表时间：
2017-02
影响因子：
4.1
通讯作者：
Jenkins MA
中科院分区：
文献类型：
--
作者：
Buchanan DD;Clendenning M;Rosty C;Eriksen SV;Walsh MD;Walters RJ;Thibodeau SN;Stewart J;Preston S;Win AK;Flander L;Ouakrim DA;Macrae FA;Boussioutas A;Winship IM;Giles GG;Hopper JL;Southey MC;English D;Jenkins MA
Tumour testing of colorectal cancers (CRC) for mismatch repair (MMR) deficiency is an effective approach to identify carriers of germline MMR gene mutation (Lynch syndrome). The aim of this study was to identify MMR gene mutation carriers in two cohorts of population-based CRC utilising a combination of tumour and germline testing approaches. CRCs from 813 patients diagnosed with CRC <60 years of age from the Australasian Colorectal Cancer Family Registry (ACCFR) and from 826 patients from the Melbourne Collaborative Cohort Study (MCCS) were tested for MMR protein expression using immunohistochemistry (IHC), microsatellite instability (MSI), BRAFV600E somatic mutation and for MLH1 methylation. MMR gene mutation testing (Sanger sequencing and MLPA) was performed on germline DNA of patients with MMR-deficient tumours and a subset of MMR-proficient CRCs. Of the 813 ACCFR probands, 90 probands demonstrated tumour MMR-deficiency (11.1%) and 42 had a MMR gene germline mutation (5.2%). For the MCCS, MMR-deficiency was identified in the tumours of 103 probands (12.5%) and 7 had a germline mutation (0.8%). All the mutation carriers were diagnosed prior to 70 years of age. Probands with a MMR-deficient CRC without MLH1 methylation and a gene mutation were considered Lynch-like and comprised 41.1% and 22.3% of the MMR-deficient CRCs for the ACCFR and MCCS, respectively. Identification of MMR gene mutation carriers in Australian CRC-affected patients is optimised by IHC screening of CRC diagnosed before 70 years. A significant proportion of MMR-deficient CRCs will have unknown aetiology (Lynch-like) proving problematic for clinical management.
登录
查看更多内容
影响因子：
45.3
作者：
Southey, MC;Jenkins, MA;Hopper, JL
通讯作者：
Hopper, JL
影响因子：
39.2
作者：
Ladabaum U;Wang G;Terdiman J;Blanco A;Kuppermann M;Boland CR;Ford J;Elkin E;Phillips KA
通讯作者：
Phillips KA
影响因子：
--
作者：
Loes, Inger Marie;Immervoll, Heike;Angelsen, Jon-Helge;Horn, Arild;Geisler, Juergen;Busch, Christian;Lonning, Per Eystein;Knappskog, Stian
通讯作者：
Knappskog, Stian
影响因子：
5.7
作者：
Estrella, Jeannelyn S.;Tetzlaff, Michael T.;Broaddus, Russell R.
通讯作者：
Broaddus, Russell R.
影响因子：
45.3
作者：
Buchanan, Daniel D.;Tan, Yen Y.;Spurdle, Amanda B.
通讯作者：
Spurdle, Amanda B.