25、Driver mutation catalogue ...
-
The 189 germline variants identified in 29 cancer predisposition genes consisted of 8 deletions and 181 point mutations.
在29个癌症易感基因中确定的189个种系变异，包括8个缺失和181个点突变。
The top five affected genes (containing nearly 80% of variants) were the well-known germline drivers CHEK2, BRCA2, MUTYH, BRCA1 and ATM.
前五位受影响的基因（包含近80%的变体）是众所周知的生殖系驱动基因CHEK2、BRCA2、MUTYH、BRCA1和ATM。
The corresponding wild-type alleles were found to be lost in the tumour sample in more than half of the cases, either by LOH or somatic point mutation, indicating a high penetrance for these variants, particularly in BRCA1, APC and BRCA2.
在半数以上的案例中，肿瘤样本中发现丢失的相应的野生型等位基因，要么LOH，要么体细胞点突变，表明这些变体具有很高的外显性，特别是在BRCA1、APC和BRCA2中。
The 276 fusions consisted of 168 in-frame coding fusions, 90 cis-activating fusions that involve repositioning of regulatory elements in 5′ genic regions, and 18 in-frame intragenic deletions in which one or more exons was deleted.
276个融合包括168个框内编码融合，90个顺式激活融合，涉及在5‘基因区域重新定位调控因子，以及18个框内基因内缺失，其中一个或多个外显子被删除。
ERG, BRAF, ERBB4, ALK, NRG1 and ETV4 were the most commonly observed 3′ partners, which together make up more than half of the fusions.
ERG、BRAF、ERBB4、ALK、NRG1和ETV4是最常见的被观察到的3‘搭配者，占融合的一半以上。
In total, 76 out of the 89 ERG fusions were TMPRSS2–ERG and affected 36% of all prostate cancer samples in the cohort.
89例ERG融合中，总计76例为TMPRSS2-ERG，影响到队列中全部前列腺癌标本的36%。
There were 146 fusion pairs not previously recorded in CGI, OncoKb, COSMIC or CIViC databases.
有146个融合对之前没有在CGI，OncoKb，CPSMIC和CIViC数据库里被记录。
We found that 71% of somatic driver point mutations in oncogenes occur at or within five nucleotides already known to pathogenic muta-tional hotspots.
我们发现71%的肿瘤基因的体细胞驱动点突变发生在致病突变热点已知的五个核苷酸上，或其内。
In the six most prevalent oncogenes (KRAS, PIK3CA, BRAF, NRAS, TERT and ESR1), the rate was 97%.
在6个最常见的癌基因(KRAS、PIK3CA、BRAF、NRAS、TERT和ESR1)中，概率为97%。
Furthermore, in many of the key oncogenes, we document several likely activating but non-canonical variants near known mutational hotspots, particularly in-frame indels.
此外，在许多关键的癌基因中，我们记录了几个可能激活但非典型的变体接近已知的突变热点，尤其是框内的插入缺失。
Despite in-frame indels being exceptionally rare overall, we found an excess in known oncogenes including PIK3CA, KIT, ERBB2 and BRAF frequently occurring at or near known hotspots.
尽管框内的插入缺失总体上异常罕见，但我们发现已知癌基因（包括PIK3CA、KIT、ERBB2和BRAF）中有过量存在，在已知的热点或是其附近。
In FOXA1, we identified ten in-frame indels that are highly enriched in prostate cancer (seven out of ten cases) and clustered at two locations that were not previously associated with pathogenic mutations.
在FOXA1中，我们发现了10个高度富集于前列腺癌的框内插入缺失（10个病例中有7个），它们聚集在两个之前与致病突变无关的位置。
作者有话说第25章 Driver mutation catalogue
