Analysis of BRCA1/2 Gene Mutation in 51 Patients with Ovarian Cancer

doi:10.12280/gjszjk.20230119

Abstract

Abstract:

Objective: To evaluate the correlation between BRCA1/2 gene mutation and clinicalcharacteristics in patients with ovarian cancer, and the effect of BRCA1/2 gene mutation on prognosis. Methods: From November 2017 to June 2022,51 patients with ovarian cancer who received BRCA1/2 gene detection in theFirst Hospital of Lanzhou University were selected as the research subjects.According to the test results, they weredivided into the BRCA1/2 mutation group(30 cases) and the BRCA1/2 non-mutation group(21 cases). Theclinical baseline data，clinicopathological features and prognosis of the two groups were compared. The relevantfactors related to the prognosis were analyzed.Results: There were no significant differences in the age of onset,BMI, family history of malignant tumor, CA 125 and HE4 before treatment between the two groups (P>0.05).Therewere significant differences in the tumor stage and lymph node metastasis between the BRCA1/2 mutation groupand the BRCA1/2 non-mutation group (P<0.05).Multivariate Cox analysis showed that the BRCA1/2 genemutation was not an independent prognostic factor for survival and PFS in ovarian cancer (HR=0.752,95%Cl.0.394-1.435，P=0.329).Conclusions: The BRCA1/2 gene mutation is an important factor in determining theclinical treatment of ovarian cancer，and it is significantly related to tumor stage and lymph node metastasis.However,the BRCA1/2 gene mutation could not be an independent risk factor for ovarian cancer.

Key words: Ovarian neoplasms, Genes, BRCA1, Genes，BRCA2, Genes, Mutation, Prognosis

GE Yam, XU Fei-xue, Ll Hong-wei, GAO Ming-xia. Analysis of BRCA1/2 Gene Mutation in 51 Patients with Ovarian Cancer[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(4): 277-281.

Figures/Tables 4

References 19

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组别	n	发病年龄（岁）		BMI（kg/m²）		恶性肿瘤家族史		治疗前CA125（U/mL）		治疗前HE4（pmol/L）
组别	n	≤50	>50	≤24	>24	有	无	≤500	>500	≤150	>150
BRCA1/2突变组	30	11（36.7）	19（63.3）	18（60.0）	12（40.0）	6（20.0）	24（80.0）	12（40.0）	18（60.0）	6（20.0）	24（80.0）
BRCA1/2正常组	21	7（33.3）	14（66.7）	17（81.0）	4（19.0）	1（4.8）	20（95.2）	9（42.9）	12（57.1）	6（28.6）	15（71.4）
χ²		0.060		2.519		2.422		0.042		0.504
P		0.806		0.112		0.120		0.838		0.478

组别	n	发病年龄（岁）		BMI（kg/m²）		恶性肿瘤家族史		治疗前CA125（U/mL）		治疗前HE4（pmol/L）
组别	n	≤50	>50	≤24	>24	有	无	≤500	>500	≤150	>150
BRCA1/2突变组	30	11（36.7）	19（63.3）	18（60.0）	12（40.0）	6（20.0）	24（80.0）	12（40.0）	18（60.0）	6（20.0）	24（80.0）
BRCA1/2正常组	21	7（33.3）	14（66.7）	17（81.0）	4（19.0）	1（4.8）	20（95.2）	9（42.9）	12（57.1）	6（28.6）	15（71.4）
χ²		0.060		2.519		2.422		0.042		0.504
P		0.806		0.112		0.120		0.838		0.478

序号	突变位点	突变方式	序号	突变位点	突变方式
BRCA1（n=17）			BRCA2（n=17）
1	NM_007294:intron21:c.5406+1G>A	剪接突变	1	NM_000059:exon:c.3794G>T:p.Cys1265Phe	错义突变
2	NM_007294:exon10:c.1058G>A:p.Trp353Ter	终止突变	2	NM_000059:exon:c.6706del:p.Glu2236Lysfs*5	移码突变
3	NM_007294:exon10:c.1312G>T:p.Glu438Ter	终止突变	3	NM_000059:exon23:c.9100C>T:p.GIn3034Ter	终止突变
4	exon18-exon19	大片段重排	4	NM_000059:exon11:c.2186T>C:p.ILe729Thr	错义突变
5	c.1325G>A	同义突变	5	NM_000059:exon14:c.7141C>T:p.Pro2381Ser	错义突变
6	c.5728-1G>C	剪接突变	6	NM_000059:exon:c.1012G>A:p.Ala338Thr	杂合突变
7	c.5470_5477delATTGGGCA	移码突变	7	c.7625C>T	同义突变
8	NM_007294:intron4c.21+1G>T	终止突变	8	NM_000059:exon11:c.2808_2811del:p.Ala938Profs*21	移码突变
9	p.pro115*（c.342_343delTC）	终止突变	9	c.9097dup	重复突变
10	c.302-2A>G	剪接突变	10	NM_000059:exon11:c.4178C>T:p.Ala1393Val	错义突变
11	c.5054C>T	错义突变	11	NM_000059:exon11:c.3191C>G:p.Ser1064Ter	终止突变
12	NM_007294:exon15:c.4713_4715del:p.Ser1572del	非移码缺失突变	12	c.9097delA	终止突变
13	c.2572C>T	无义突变	13	c.3794G>A	终止突变
14	c.1396delC	移码突变	14	NM_007294:c.3649del:p.Ser1217Leufs*18	移码突变
15	c.3113A>G	错义突变	15	c.865A>C	错义突变
16	c.4900A>G	错义突变	16	NM_000059:exon11:c.5959C>T:p.GIn1987Ter	终止突变
17	c.2008delG	移码突变	17	c.5320C>T	错义突变

序号	突变位点	突变方式	序号	突变位点	突变方式
BRCA1（n=17）			BRCA2（n=17）
1	NM_007294:intron21:c.5406+1G>A	剪接突变	1	NM_000059:exon:c.3794G>T:p.Cys1265Phe	错义突变
2	NM_007294:exon10:c.1058G>A:p.Trp353Ter	终止突变	2	NM_000059:exon:c.6706del:p.Glu2236Lysfs*5	移码突变
3	NM_007294:exon10:c.1312G>T:p.Glu438Ter	终止突变	3	NM_000059:exon23:c.9100C>T:p.GIn3034Ter	终止突变
4	exon18-exon19	大片段重排	4	NM_000059:exon11:c.2186T>C:p.ILe729Thr	错义突变
5	c.1325G>A	同义突变	5	NM_000059:exon14:c.7141C>T:p.Pro2381Ser	错义突变
6	c.5728-1G>C	剪接突变	6	NM_000059:exon:c.1012G>A:p.Ala338Thr	杂合突变
7	c.5470_5477delATTGGGCA	移码突变	7	c.7625C>T	同义突变
8	NM_007294:intron4c.21+1G>T	终止突变	8	NM_000059:exon11:c.2808_2811del:p.Ala938Profs*21	移码突变
9	p.pro115*（c.342_343delTC）	终止突变	9	c.9097dup	重复突变
10	c.302-2A>G	剪接突变	10	NM_000059:exon11:c.4178C>T:p.Ala1393Val	错义突变
11	c.5054C>T	错义突变	11	NM_000059:exon11:c.3191C>G:p.Ser1064Ter	终止突变
12	NM_007294:exon15:c.4713_4715del:p.Ser1572del	非移码缺失突变	12	c.9097delA	终止突变
13	c.2572C>T	无义突变	13	c.3794G>A	终止突变
14	c.1396delC	移码突变	14	NM_007294:c.3649del:p.Ser1217Leufs*18	移码突变
15	c.3113A>G	错义突变	15	c.865A>C	错义突变
16	c.4900A>G	错义突变	16	NM_000059:exon11:c.5959C>T:p.GIn1987Ter	终止突变
17	c.2008delG	移码突变	17	c.5320C>T	错义突变

组别	n	肿瘤分期			肿瘤分级				淋巴结转移				病理类型
组别	n	Ⅰ~Ⅱ期	Ⅲ~Ⅳ期		G1~G2		G3~G4		是		否		浆液性腺癌		其他
BRCA1/2突变组	30	3（10.0）	27（90.0）		17（56.7）		13（43.3）		19（63.3）		11（36.7）		23（76.7）		7（23.3）
BRCA1/2正常组	21	8（38.1）	13（61.9）		15（71.4）		6（28.6）		6（28.6）		15（71.4）		15（71.4）		6（28.6）
χ²		5.764			1.152				5.973				0.178
P		0.016			0.283				0.015				0.673
组别	n	化疗方案				是否铂敏感复发*				1年生存情况				2年生存情况
组别	n	紫杉醇+铂类		多西他赛+铂类		是		否		是		否		是		否
BRCA1/2突变组	30	18（60.0）		12（40.0）		14（82.4）		3（17.6）		28（93.3）		2（6.7）		23（76.7）		7（23.3）
BRCA1/2正常组	21	15（71.4）		6（28.6）		5（55.6）		4（44.4）		21（100.0）		0（0.0）		17（81.0）		4（19.0）
χ²		0.706				2.148				1.457				0.134
P		0.401				0.143				0.227				0.714