遗传性乳腺癌-卵巢癌综合征与散发性卵巢癌患者BRCA基因致病性突变表型的差异  

Comparison of hereditary breast and ovarian cancer syndrome and sporadic ovarian cancer in ovarian cancer BRCA mutations

作　　者：段荣荣 孙立新[2] 赵宏伟[2] Duan Rongrong;Sun Lixin;Zhao Hongwei(Department of Obstetrics and Gynecology,Graduate School,Shanxi Medical University,Taiyuan 030000,China;Department of Gynecology,Shanxi Provincial Cancer Hospital,Taiyuan 030000,China)

机构地区：[1]山西医科大学研究生院妇产科学系,太原030000 [2]山西省肿瘤医院妇科,太原030000

出　　处：《中华妇产科杂志》2021年第11期788-795,共8页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的探讨BRCA基因致病性突变表型在遗传性乳腺癌-卵巢上皮性癌(卵巢癌;HBOC)综合征与散发性卵巢癌(SOC)患者中的差异。方法本研究为探索性研究,纳入标准是2018年11月至2019年12月山西省肿瘤医院收治的284例未经选择(指连续性病例)的卵巢癌患者,行高通量DNA测序,测序范围包括BRCA1和BRCA2基因全编码区、外显子-内含子连接区、非翻译区、启动子区。收集BRCA基因致病性突变的卵巢癌患者,进行突变位点分析,比较HBOC综合征与SOC患者BRCA基因致病性突变表型的差异。结果(1)284例卵巢癌患者中,BRCA基因致病性突变者77例,突变率为27.1%(77/284),其中BRCA1基因突变率为19.7%(56/284)、BRCA2基因突变率为6.7%(19/284)、BRCA1/2基因共同突变率为0.7%(2/284)。284例卵巢癌患者中,73例HBOC综合征患者的BRCA基因致病性突变率为43.8%(32/73),显著高于211例SOC患者的突变率[21.3%(45/211);χ^(2)=13.905,P<0.01];其中,BRCA1基因突变率HBOC综合征患者高于SOC患者[分别为87.5%(28/32)、62.2%(28/45)],BRCA2基因突变率HBOC综合征患者低于SOC患者[分别为6.2%(2/32)、37.8%(17/45)],分别比较,差异均有统计学意义(P均<0.05)。77例BRCA基因致病性突变患者中,75例患者为1个位点突变,2例为多个位点突变(包括1例同时2个位点突变、1例同时3个位点突变),共有突变位点80个,突变类型以移码突变(55.0%,44/80)和无义突变(31.2%,25/80)为主。(2)73例HBOC综合征患者中,存在BRCA基因致病性突变者32例,其中突变发生于BRCA1基因者28例,主要位于BRCA1基因外显子11和24(分别为9、7例);而突变发生于BRCA2基因者仅2例,均位于BRCA2基因外显子11;另有2例为多个位点突变。211例SOC患者中,存在BRCA基因致病性突变者45例,其中突变发生于BRCA1基因者28例,主要位于BRCA1基因为外显子11和24(分别为15、2例);突变发生于BRCA2基因者17例,主要位于BRCA2基因外显子11(11例)。(3)本研究新发现BRCA�Objective To study the difference between BRCA gene mutations in hereditary breast and ovarian cancer syndrome(HBOC)and in sporadic ovarian cancer(SOC).Methods This study was for exploratory research,the inclusion criteria were 284 patients with ovarian cancer admitted at Shanxi Provincial Cancer Hospital from November 2018 to December 2019,with high-throughput DNA sequencing including the full coding regions and exon-intron link regions of BRCA1 and BRCA2 gene.Pathogenic mutations in the BRCA gene of patients with ovarian cancer were collected and mutation site analysis was performed to compare phenotypic differences in pathogenic mutations between HBOC syndrome and SOC patients.Results(1)Of the 284 ovarian cancer patients,seventy-seven had BRCA pathogenic mutations with a mutation rate of 27.1%(77/284),with BRCA1 mutation rate of 19.7%(56/284),BRCA2 gene 6.7%(19/284)and BRCA1/2 common mutation rate of 0.7%(2/284).Of the 284 patients with ovarian cancer,the pathogenic mutation rate in the BRCA gene in HBOC syndrome patients was 43.8%(32/73),which were significantly higher than that in SOC patients[21.3%(45/211);χ^(²)=13.905,P<0.01].Among BRCA1 gene mutation,the mutation rate in HBOC syndrome was higher than that of SOC[87.5%(28/32)vs 62.2%(28/45)],the BRCA2 gene mutation rate in patients with HBOC syndrome was lower than that in SOC patients[6.2%(2/32)vs 37.8%(17/45)],and there were statistically significant differences(all P<0.05).Two of the 77 patients with pathogenic mutations in the BRCA gene were multisite mutations,including one simultaneous two site mutation,one simultaneous three site mutation.There were 80 mutation sites with frameshift deletion mutations(55.0%,44/80)and nonsense mutations(31.2%,25/80).(2)Of the 73 patients with HBOC syndrome,32 cases had pathogenic mutations in BRCA gene,including 28 cases in BRCA1,mainly in exon 11 and 24(9 and 7 cases,respectively),and only two cases in BRCA2,both in exon 11;another two had multiple locus mutations.Of the 211 patients with SOC,45 cases had pathogen

关 键 词：遗传性乳腺癌和卵巢癌综合征 卵巢肿瘤 基因 BRCA1 基因 BRCA2 突变 

分 类 号：R737.31[医药卫生—肿瘤]