Analysis of BRCA Gene Mutation Status and Clinical Significance in 74 Patients with Epithelial Ovarian Cancer

doi:10.12280/gjfckx.20210068

Abstract

Abstract:

Objective： To analyze BRCA germline mutation in patients with epithelial ovarian cancer (EOC) and its relationship with clinical pathological features. Methods： The BRCA germline mutation results of 74 patients with EOC who received therapy at Tianjin Central Hospital of Gynecology Obstetrics from January 2017 to January 2020 were collected. Statistical analysis was performed on the relationship between BRCA mutation and clinical pathological features. Results： In 74 patients of EOC, the mutation rate of BRCA1 and BRCA2 were 24.3% and 9.5% respectively. The main mutation mode includes 15 cases of frame shift mutations and 5 cases of nonsense mutations. The mutations are mainly appears in the exon coding region (CDS9 and CDS10). There was no significant difference in the FIGO stage, pathological type, lymphatic metastasis status, serum levels of CA-125, family history of malignant tumor between BRCA-mutated patients and wild-type patients in this study (P>0.05). The recurrence-free survival (RFS) of patients with BRCA-mutated is longer than that of patients without BRCA-mutated, and the difference is statistically significant (Z=-1.931, P=0.027). Statistically significant correlations were observed between BRCA-mutated status and family history of hereditary breast cancer ovarian cancer syndrome (HBOC) ( χ ²=4.059, P=0.044). Conclusions： All female members of the family of EOC patients with family history of HBOC should undergo BRCA gene testing, which is an effective way to screen high-risk patients for ovarian cancer.

Key words: Ovarian neoplasms, Hereditary breast and ovarian cancer syndrome, Genes,BRCA1, Genes,BRCA2, Mutation, Epithelial ovarian cancer

RAO Yang, LI Xiao, XU De-huan, ZHU Xue-ping, QU Peng-peng. Analysis of BRCA Gene Mutation Status and Clinical Significance in 74 Patients with Epithelial Ovarian Cancer[J]. Journal of International Obstetrics and Gynecology, 2021, 48(3): 351-355.

Figures/Tables 3

References 20

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序号	BRCA	年龄（岁）	基因亚区	突变方式	核苷酸	氨基酸
1	1	55	CDS9	框移突变	c.3329_3330insA	p.Gln1111Alafs*4
2	1	52	CDS9	框移突变	c.1961_1962insA	p.Tyr655Valfs*18
3	1	51	CDS18	无义突变	Tc.5251C>T	p.Arg1751Ter
4	1	62	CDS22	框移突变	c.5470_5477delATTGGGCA	p.Ile1824AspfsX3
5	1	51	CDS22	框移突变	c.5470_5477delATTGGGCA	p.Ile1824AspfsX3
6	1	62	CDS9	无义突变	c.1465G>T	p.Glu489Terp
7	1	63	Intron16	剪接突变	c.5075-1delG	-
8	1	62	CDS9	框移突变	c.677delG	p.Cys226Leufs*8
9	1	62	EX23	框移突变	c.5470_5477delATTGGGCA	p.Ile1824Aspfs*3
10	1	38	CDS9	框移突变	c.3442delG	p.Glu1148Arg
11	1	38	CDS16	错义突变	c.5123C>A	p.Ala1708Glu
12	1	45	EX11	框移突变	c.1504_1508delTTAAA	p.Leu502Alafs*2
13	1	46	CDS15	错义突变	c.5054C>T	p.Thr1685Ile
14	1	48	CDS9	无义突变	c.3122C>G	p.Ser1041*
15	1	49	EX1_24	缺失突变	EX1_24 DEL	-
16	1	50	CDS10	无义突变	c.1300A>T	p.Lys434
17	1	51	CDS11	框移突变	c.3719dupT	p.Phe1241fs
18	1	47	CDS17	错义突变	c.5089T>C	p.Cys1697Arg
19	2	44	CDS10	框移突变	c.6591_6592delTG	p.Glu2198Asnfs*4
20	2	51	CDS9	框移突变	c.1318_1321delCTTA	p.Thr441Glnfs*18
21	2	72	CDS10	框移突变	c.6367_6368insc.A	p.Thr2125Asnfs*4
22	2	43	CDS10	框移突变	c.5984delA	p.Asn1995Thrfs*9
23	2	52	EX11	无义突变	c.6415G>T	p.Glu2139
24	2	52	CDS10	框移突变	c.6441_6442delCT	p.Ser2148Tyrfs*2
25	2	46	CDS10	框移突变	c.6149dupT	p.Asn2051LysfsTer*9

序号	BRCA	年龄（岁）	基因亚区	突变方式	核苷酸	氨基酸
1	1	55	CDS9	框移突变	c.3329_3330insA	p.Gln1111Alafs*4
2	1	52	CDS9	框移突变	c.1961_1962insA	p.Tyr655Valfs*18
3	1	51	CDS18	无义突变	Tc.5251C>T	p.Arg1751Ter
4	1	62	CDS22	框移突变	c.5470_5477delATTGGGCA	p.Ile1824AspfsX3
5	1	51	CDS22	框移突变	c.5470_5477delATTGGGCA	p.Ile1824AspfsX3
6	1	62	CDS9	无义突变	c.1465G>T	p.Glu489Terp
7	1	63	Intron16	剪接突变	c.5075-1delG	-
8	1	62	CDS9	框移突变	c.677delG	p.Cys226Leufs*8
9	1	62	EX23	框移突变	c.5470_5477delATTGGGCA	p.Ile1824Aspfs*3
10	1	38	CDS9	框移突变	c.3442delG	p.Glu1148Arg
11	1	38	CDS16	错义突变	c.5123C>A	p.Ala1708Glu
12	1	45	EX11	框移突变	c.1504_1508delTTAAA	p.Leu502Alafs*2
13	1	46	CDS15	错义突变	c.5054C>T	p.Thr1685Ile
14	1	48	CDS9	无义突变	c.3122C>G	p.Ser1041*
15	1	49	EX1_24	缺失突变	EX1_24 DEL	-
16	1	50	CDS10	无义突变	c.1300A>T	p.Lys434
17	1	51	CDS11	框移突变	c.3719dupT	p.Phe1241fs
18	1	47	CDS17	错义突变	c.5089T>C	p.Cys1697Arg
19	2	44	CDS10	框移突变	c.6591_6592delTG	p.Glu2198Asnfs*4
20	2	51	CDS9	框移突变	c.1318_1321delCTTA	p.Thr441Glnfs*18
21	2	72	CDS10	框移突变	c.6367_6368insc.A	p.Thr2125Asnfs*4
22	2	43	CDS10	框移突变	c.5984delA	p.Asn1995Thrfs*9
23	2	52	EX11	无义突变	c.6415G>T	p.Glu2139
24	2	52	CDS10	框移突变	c.6441_6442delCT	p.Ser2148Tyrfs*2
25	2	46	CDS10	框移突变	c.6149dupT	p.Asn2051LysfsTer*9

组别	n	年龄（岁）	FIGO分期		病理类型			淋巴结转移		HBOC家族史		恶性肿瘤家族史
组别	n	年龄（岁）	Ⅰ~Ⅱ	Ⅲ~Ⅳ	高级别浆液性	黏液性	其他类型*	有	无	有	无	有	无
突变组	25	54.2±9.3	7（28.0）	18（72.0）	23（92.0）	0（0.0）	2（8.0）	16（64.0）	9（36.0）	10（40.0）	15（60.0）	15（60.0）	10（40.0）
野生组	49	52.5±8.1	13（26.5）	36（73.5）	39（79.6）	2（4.1）	8（16.3）	21（42.9）	28（57.1）	9（18.4）	40（81.6）	26（53.1）	23（46.9）
t或χ²		0.658	0.018			7.144		2.960		4.059		0.323
P		0.355	0.893			0.128		0.085		0.044		0.570

组别	n	年龄（岁）	FIGO分期		病理类型			淋巴结转移		HBOC家族史		恶性肿瘤家族史
组别	n	年龄（岁）	Ⅰ~Ⅱ	Ⅲ~Ⅳ	高级别浆液性	黏液性	其他类型*	有	无	有	无	有	无
突变组	25	54.2±9.3	7（28.0）	18（72.0）	23（92.0）	0（0.0）	2（8.0）	16（64.0）	9（36.0）	10（40.0）	15（60.0）	15（60.0）	10（40.0）
野生组	49	52.5±8.1	13（26.5）	36（73.5）	39（79.6）	2（4.1）	8（16.3）	21（42.9）	28（57.1）	9（18.4）	40（81.6）	26（53.1）	23（46.9）
t或χ²		0.658	0.018			7.144		2.960		4.059		0.323
P		0.355	0.893			0.128		0.085		0.044		0.570