The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer.
The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer.
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BRCA2缺陷的原发性和转移性前列腺癌的肿瘤突变景观。
DOI：
10.1038/s41698-022-00284-6
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发表时间：
2022-06-17
影响因子：
7.9
通讯作者：
中科院分区：
文献类型：
--
作者：
生殖系BRCA 2致病序列变异的携带者具有升高的侵袭性前列腺癌风险，并且是精确肿瘤治疗的候选者。我们研究了BRCA 2缺陷型（BRCA 2d）前列腺肿瘤与BRCA 2完整型（BRCA 2 i）肿瘤相比是否有明显的基因组改变。在ICGC、GENIE和TCGA数据库的2536例原发性和899例转移性前列腺肿瘤中，我们确定了138例原发性和85例转移性BRCA 2d肿瘤。总肿瘤突变负荷（TMB）在原发性BRCA 2d肿瘤中较高，尽管致病性TMB在肿瘤BRCA 2状态之间没有差异。BRCA 2d原发性肿瘤中KMT 2D的致病性和总单核苷酸变异（SNV）频率较高，BRCA 2d转移性肿瘤中KMT 2D的总SNV频率也较高。NEK 3、RB 1和APC的纯合缺失在BRCA 2d原发性肿瘤中富集，RB 1缺失在转移性BRCA 2d肿瘤中也富集。TMPRSS 2-ETV 1融合在BRCA 2d肿瘤中更常见。这些结果确定了标志BRCA 2d和BRCA 2 i前列腺肿瘤之间病因学和预后差异的体细胞改变。
Carriers of germline BRCA2 pathogenic sequence variants have elevated aggressive prostate cancer risk and are candidates for precision oncology treatments. We examined whether BRCA2-deficient (BRCA2d) prostate tumors have distinct genomic alterations compared with BRCA2-intact (BRCA2i) tumors. Among 2536 primary and 899 metastatic prostate tumors from the ICGC, GENIE, and TCGA databases, we identified 138 primary and 85 metastatic BRCA2d tumors. Total tumor mutation burden (TMB) was higher among primary BRCA2d tumors, although pathogenic TMB did not differ by tumor BRCA2 status. Pathogenic and total single nucleotide variant (SNV) frequencies at KMT2D were higher in BRCA2d primary tumors, as was the total SNV frequency at KMT2D in BRCA2d metastatic tumors. Homozygous deletions at NEK3, RB1, and APC were enriched in BRCA2d primary tumors, and RB1 deletions in metastatic BRCA2d tumors as well. TMPRSS2-ETV1 fusions were more common in BRCA2d tumors. These results identify somatic alterations that hallmark etiological and prognostic differences between BRCA2d and BRCA2i prostate tumors.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
11.5
作者：
Henrique, Rui;Ribeiro, Franclim R.;Jeronimo, Carmen
通讯作者：
Jeronimo, Carmen
影响因子：
11.5
作者：
Chakraborty, Goutam;Armenia, Joshua;Kantoff, Philip W.
通讯作者：
Kantoff, Philip W.
影响因子：
3.3
作者：
Ittmann, MM;Wieczorek, R
通讯作者：
Wieczorek, R