Determining homologous recombination deficiency scores with whole exome sequencing and their association with responses to neoadjuvant chemotherapy in breast cancer.
Determining homologous recombination deficiency scores with whole exome sequencing and their association with responses to neoadjuvant chemotherapy in breast cancer.
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用全外显子组测序确定同源重组缺陷评分及其与乳腺癌新辅助化疗反应的关系。
DOI：
10.1016/j.tranon.2020.100986
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发表时间：
2021-03
影响因子：
5
通讯作者：
Shimazu K
中科院分区：
文献类型：
--
作者：
Kim SJ;Sota Y;Naoi Y;Honma K;Kagara N;Miyake T;Shimoda M;Tanei T;Seno S;Matsuda H;Noguchi S;Shimazu K
全外显子组测序可以评估乳腺癌中的HRD状态以及SNP阵列。生殖系HRR基因突变的肿瘤HRD评分高于体细胞HRR基因突变的肿瘤和野生型HRR基因的肿瘤，两者之间没有发现差异。即使在体细胞HRR基因突变的肿瘤中，获得洛也会导致HRD状态。在管腔亚组中，HRD高的肿瘤与新辅助紫杉醇随后5-氟尿嘧啶/表阿霉素/环磷酰胺的良好反应相关。最近的研究表明，同源修复缺陷（HRD）评分是一个有用的标志物的反应，聚（ADP-核糖）聚合酶抑制剂或铂为基础的化疗。我们确定了HRD评分，并阐明了HRD高肿瘤的临床病理特征及其对非铂类化疗的反应。原发性乳腺癌患者（n = 120）术前接受紫杉醇治疗，随后接受5-氟尿嘧啶/表阿霉素/环磷酰胺（P-FEC）治疗。使用全外显子组测序（WES）分析化疗前获得的肿瘤组织中的生殖系和体细胞同源重组相关基因突变（分别为gHRRm和sHRRm）和HRD评分。在120个肿瘤中，30个被确定为HRD高肿瘤，与高Ki-67（P = 0.014）、ER阴性（P = 0.007）和PR阴性（P = 0.021）显著相关。三阴性癌症的HRD评分显著高于管腔型、管腔型-HER 2和HER 2亚型（分别为P = 0.023、0.016和0.033）。携带gHRRm的肿瘤HRD评分显著高于携带sHRRm（P = 0.002）或野生型HRR基因的肿瘤（P = 1.44e-4），但携带sHRRm和野生型HRR基因的肿瘤HRD评分无显著差异（P = 0.206）。在所有肿瘤和管腔亚型中，与HRD低肿瘤相比，HRD高肿瘤的pCR率和近pCR率分别显著较高（P = 0.003）和较高（P = 0.049）。高HRD肿瘤与侵袭性表型和gHRRm相关，但与sHRRm无关。我们的研究结果表明，HRD评分可能有助于预测管腔亚型对P-FEC的反应。
Whole exome sequencing can assess HRD status as well as the SNP array in breast cancer. HRD scores were higher in tumors with the germline HRR gene mutations than in those with the somatic HRR gene mutations and the wild-type HRR genes, between which no difference was found. Acquisition of LOH induced HRD status even in tumor with the somatic HRR gene mutations. In the luminal subset, HRD-high tumors were associated with a favorable response to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide. Recent studies demonstrated that homologous repair deficiency (HRD) score is a useful marker for response to poly (ADP-ribose) polymerase inhibitors or platinum-based chemotherapy. We determined HRD scores and elucidated the clinicopathologic characteristics of HRD-high tumors and their response to non-platinum-based chemotherapy. Primary breast cancer patients (n = 120) were pre-operatively treated with paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC). Germline and somatic homologous recombination related gene mutations (gHRRm and sHRRm, respectively) and HRD scores were analyzed using whole exome sequencing (WES) in tumor tissues obtained before chemotherapy. Of 120 tumors, 30 were determined to be HRD-high tumors, significantly associated with high Ki-67 (P = 0.014), ER negativity (P = 0.007), and PR negativity (P = 0.021). Triple-negative cancers showed significantly higher HRD scores than the luminal, luminal-HER2, and HER2 subtypes (P = 0.023, 0.016, and 0.033, respectively). HRD scores were significantly higher in tumors with gHRRm than in those with sHRRm (P = 0.002) or wild-type HRR genes (P = 1.44e-4), but no significant difference was found in HRD scores between tumors with sHRRm and wild-type HRR genes (P = 0.206). HRD-high tumors had significantly (P = 0.003) higher pCR rates and higher near-pCR rates (P = 0.049) compared with those of the HRD-low tumors in all tumors and the luminal subtype, respectively. HRD-high tumors were associated with aggressive phenotypes and gHRRm, but not sHRRm. Our findings suggested that HRD scores might be useful in predicting response to P-FEC in the luminal subtype.
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影响因子：
19
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
通讯作者：
D'Andrea AD
DOI：
10.1093/annonc/mdu479
发表时间：
2015-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Favero F;Joshi T;Marquard AM;Birkbak NJ;Krzystanek M;Li Q;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
将基于SNP阵列的同源重组缺乏措施迁移到下一代乳腺癌数据。
影响因子：
5.9
作者：
Sztupinszki Z;Diossy M;Krzystanek M;Reiniger L;Csabai I;Favero F;Birkbak NJ;Eklund AC;Syed A;Szallasi Z
通讯作者：
Szallasi Z
DOI：
10.1002/path.4890
发表时间：
2017-06
期刊：
The Journal of pathology
影响因子：
--
作者：
Mutter RW;Riaz N;Ng CK;Delsite R;Piscuoglio S;Edelweiss M;Martelotto LG;Sakr RA;King TA;Giri DD;Drobnjak M;Brogi E;Bindra R;Bernheim G;Lim RS;Blecua P;Desrichard A;Higginson D;Towers R;Jiang R;Lee W;Weigelt B;Reis-Filho JS;Powell SN
通讯作者：
Powell SN
影响因子：
64.8
作者：
Jonsson, Philip;Bandlamudi, Chaitanya;Taylor, Barry S.
通讯作者：
Taylor, Barry S.