BRCA1,BRCA2基因与乳腺癌,卵巢癌多发家族

目前研究普遍认为,ＢＲＣＡ１,ＢＲＣＡ２基因属抑癌基因,这些基因的某些突变型的携带,患乳腺癌,卵巢癌等恶性肿瘤的危险性显增高,本介绍了ＢＲＣＡ１,ＢＲＣＡ２基因定位和克隆后,近年来对上述基因相关家族的特点,基因外显率,抑癌机制,基因突变热点,突变类型的种族特异性等方面的研究进展,介绍了肿瘤高度和中度危险家族的划分方法和意义,并分析了今后我国在相关领域深入研究的思路。     

50例中国男性乳腺癌临床特征和遗传学病因

目的拟通过男性乳腺癌(MBC)病例报道,为中国MBC的精准诊疗提供了依据。方法回顾了2015年至2019年北京市两家肿瘤专科医院收治的50例MBC患者的人口学特征、临床和病理特征、治疗及随访情况。进一步对于其中25例MBC患者进行了乳腺癌易感基因1号和2号(BRCA1/2)等基因的二代测序。结果入组MBC患者平均发病年龄为(58±11.5)岁,超重和肥胖患者占60.00%,绝大部分MBC患者为雄激素受体阳性(95.24%)和雌激素受体阳性(89.36%),而三阴性乳腺癌比例(10.64%)较国外更高。在治疗方面,保乳术(6.12%)和前哨淋巴结活检(26.53%)比例相对较低,内分泌治疗(84.00%)在术后辅助治疗中占重要地位,但术后辅助放疗(20.00%)和化疗(52.00%)相对不足。此外,在接受基因检测患者中有2例(8.00%)患者存在BRCA1/2致病性突变。结论 MBC患者的临床特征和遗传学病因具有一定特殊性。在治疗方面,手术方式可以进一步做"减法",而术后辅助放疗和化疗则应作"加法"。     

三阴性乳腺癌患者BRCA1和BRCA2基因突变的临床特征及预后因素

目的:探究三阴性乳腺癌患者BRCA1和BRCA2基因突变检测的临床意义及预后因素分析.方法:研究对象选取为2003年1月至2015年12月之间的三阴性乳腺癌156例,所有患者均通过PCR法和DNA序列测定检验BRCA1和BRCA2基因突变情况,分析乳腺癌患者BRCA1和BRCA2基因突变特点.应用Log-Rank检验对BRCA1和/或BRCA2基因突变的三阴性乳腺癌患者的各项指标如年龄、ECOG状态、临床分期、淋巴结阳性数、月经状态和给药方式进行单因素分析.应用Cox风险比例回归模型分析患者年龄、ECOG状态、临床分期、淋巴结阳性数、肿瘤大小、月经状态和给药方式等多因素分析.结果:三阴乳腺癌患者发生基因突变21例,总体发生率13.46％,BRCA1突变15例,BRCA2突变6例.Log-Rank检验结果显示,发病年龄越大,ECOG评分越高,临床分期越晚,淋巴结阳性数越多,预后越差(P＜0.05),而发病时月经状态和给药方式与预后无关.COX风险比例回归模型显示,肿瘤大小(相对危险度,3.163;95％CI:1.455～9.287;P＜0.05)和淋巴结转移数(相对危险度,1.859;95％CI:1.254～6.875;P＜0.05)是BRCA基因突变三阴性乳腺癌独立的预后因素.结论:BRCA1和BRCA2基因突变可能与乳腺癌尤其是三阴乳腺癌可能有着密切的相关性,发病年龄、ECOG评分,临床分期和淋巴结阳性数及肿瘤大小与BRCA基因突变的三阴乳腺癌预后有关.     

男性乳腺发育症临床病理分析及雌,孕激素受体检测

对１１３例男性乳腺发育症进行临床病理分析。同时检测其中３０例乳腺组织中雌激素受体和孕激素受体分布情况，结果发现两者阳性率分别为８０．０％和８３．３３％。结合文献讨论了男性乳腺发育症的发生与高血清激素浓度及乳腺组织高受体水平的关系。     

一例男性乳腺癌的罕见 BRCA2基因胚系变异分析

目的:对1例男性乳腺癌患者的基因组变异进行分析,为检测后的遗传咨询提供依据。方法:检测前了解家族史、医疗史,告知被检者检测潜在的风险及可能的检测结果,利用二代测序技术对先证者进行全外显子组检测,应用Sanger测序对先证者及家系成员进行变异位点验证。结果:二代测序结果显示先证者 BRCA2基因存在c.601...     

中国上海家族性乳腺癌BRCA1和BRCA2基因的突变

目的研究上海地区家族性乳腺癌中BRCA1／BRCA2基因的突变位点及携带情况。方法研究对象来自35个汉族家族性乳腺癌家系，家系中至少有一个一级亲属乳腺癌患病史。共35例患者，其中13例发病年龄≤加岁。由静脉血提取基因组DNA，对BRCA1／BRCA2基因的全部编码序列进行扩增。扩增产物突变分析先由变性高效液相色谱分析进行筛查，之后进行DNA直接测序证实。结果在BRCA1基因中发现有4个突变位点，其中2个为新发现位点——拼接点突变（IVS17-1G〉T；IVS21＋1G〉C）；另两个为已报道的致病突变位点——移码突变（1100delAT；5640delA）。BRCA2基因的1个致病突变位点位于11号外显子上，为移码突变（5802delAATT）。另外，共发现有12个新的单核苷重复多态位点，都未引起氨基酸编码改变；其中，8个在BRCA1基因上，4个在BRCA2基因上。在家族性乳腺癌中，BRCA1突变频率（11．4％）高于BRCA2基因（2．9％）。结论新发现的2个BRCA1基因的拼接点突变可能是中国上海人群家族性乳腺癌的特有突变位点；在我国上海地区人群中，BRCA1基因突变起着比BRCA2基因更大的作用；该研究丰富了中国人群中BRCA基因的突变谱，并为未来的临床基因检测提供了筛查模式。     

海南西部地区乳腺癌患者 BRCA1 / 2 基因突变状态分析

目的 不同的区域及种族的 BRCA1 / 2 基因突变频率差异较大, 着重分析海南西部地区乳腺癌患 者 BRCA1 / 2 基因的突变状态及对患者预后的影响。 方法 选取 2015 年 10 月 ~ 2020 年 12 月在海南西部中 心医院住院并确诊为原发性乳腺癌的 256 例患者为研究对象, 采用变性高效液相色谱法 ( denaturing high performance liquid chromatography, DHPLC) 筛查乳腺癌患者是否存在 BRCA1 / 2 基因突变, 分析 BRCA1 / 2 基 因突变状态及 BRCA1 / 2 基因突变患者的临床特征, 并随访分析患者 5 年生存情况, COX 回归分析影响患者 预后的因素。 结果 256 例乳腺癌患者中共检出 53 例患者发生 BRCA1 / 2 基因突变, 其中 BRCA1 突变率 12. 11 % (31 / 256), BRCA2 突变率 8. 59 % (22 / 256), 其中有害变异率为 7. 03 % (18 / 256)。 BRCA1 / 2 基 因突变患者家族病史、 妇科疾病史、 乳腺疾病史、 雌激素受体 (estrogen receptor, ER)、 原癌基因 (CerbB2) 蛋白阳性比例以及临床病理分级、 临床分期与未突变患者比较差异有统计学意义 (P< 0. 05)。 患者总 体生存率为 83. 59 % , BRCA1 / 2 基因突变者生存率低于未突变者 (P< 0. 05), COX 回归分析显示, BRCA1 / 2 基因突变、 乳腺疾病史、 临床分期、 CerbB-2 阳性、 CEA、 CA199 均是影响乳腺癌患者生存的危险因素 (P< 0. 05)。 结论 通过 DHPLC 可有效筛查海南西部地区乳腺癌患者 BRCA1 / 2 基因的有害变异, BRCA1 / 2 基因突变与临床病理特征及预后密切相关。     

乳腺癌相关基因的研究进展

从 2 0世纪 70年代起 ,原为乳腺癌低发区的亚洲国家发病率逐年升高 ,在我国特别是北京、上海等发达城区已成为危害妇女健康主要恶性肿瘤。乳腺癌病因尚不十分清楚 ,发病机理非常复杂 ,影响乳腺癌发病因素较多。随着分子生物学的飞速发展与各种高新生物技术不断涌现 ,近年来尤为瞩目的基因组学、蛋白质组学、生物信息学、组合化学、生物芯片技术和自动化筛选技术的发展与广泛应用 ,人类基因组计划的初步完成 ,对恶性肿瘤发生、演进机理有了较深入的了解 ,防治水平不断提高。而DNA重组、基因打靶、转基因动物等众多新技术在肿瘤研究中的应用 ,使人们越来越深刻地认识到肿瘤是一种基因的疾病。本文就目前研究较多的HER2、BRCA1从基因定位、结构、执行功能的分子机制及在乳腺癌中的作用等方面进行了总结 ,以便使我们更全面地认识这些基因及其表达产物的生理、病理生理作用 ,为肿瘤防治提供更为全面、准确的信息     

中国乳腺癌患者BRCA1基因的频发突变5589del8

目的研究在中国大陆乳腺癌人群中是否存在BRCAI／2基因突变的“热点”。方法研究对象为来自全国4个乳腺癌医疗中心的177例家族性和早发性乳腺癌患者和426例散发性乳腺癌患者,根据前期研究中已发现的BRCAI／2基因突变位点,应用变性高效液相色谱分析和DNA测序技术对这些患者进行已知位点的突变检测。结果在前期研究的70例家族性和早发性乳腺癌患者和本研究的177例患者（共247例）中,共发现3例BRCAl5589del8突变的携带者,在426例散发性乳腺癌患者中也发现了2例BRCAl5589del8突变的携带者。单倍型分析的结果显示这5例患者具有相近甚至相同的单倍型。结论BRCAl5589del8突变是中国人群中BRCAl基因的频发突变,它是否是中国人群中的“始祖突变”仍需进一步研究证实。     

新疆地区维吾尔族乳腺癌BRCA1基因突变分析

目的研究新疆地区维吾尔族乳腺癌患者BRCA1基因突变情况及突变位置。方法选取70例维吾尔族乳腺癌根治标本,对照组为32例维汉族乳腺良性病变（纤维腺病及纤维腺瘤）及乳腺癌旁非癌组织;应用PCR-单链构象多态性和DNA序列测定的方法检测BRCA1基因突变。结果（1）70例维吾尔族乳腺癌中发现9例BRCA1突变的12个新位点。（2）70例维吾尔族乳腺癌BRCA1的突变率为12.86%（9/70）,22例维吾尔族早发性乳腺癌（≤35岁）BRCA1突变率为31.82%（7/22）。维吾尔族早发性乳腺癌BRCA1突变率（7/22）高于维吾尔族晚发性乳腺癌（2/48）,差异有统计学意义（χ^2=10.295,P〈0.01）。（3）70例维吾尔族乳腺癌中发现9例BRCA1基因核苷酸多态性位点,其中8例多态性位点均为3232A〉G。（4）2例双侧乳腺癌中均检测出BRCA1基因的突变。结论BRCA1突变可能与新疆维吾尔族乳腺癌尤其是维吾尔族早发性乳腺癌及双侧乳腺癌的发生密切相关。     

XX Male with breast cancer

We present the case of a 66-year-old XX male who developed breast cancer on the left side at the age of 61. His clinical, endocrinological and cytogenetic features are described. The presence of hypospadias and cancer in the left breast are noteworthy; the latter is very rarely found in Klinefelter syndrome patients. An outline of the pathogenesis of breast cancer in XX male patients is also given. This is the first report of an XX male with breast cancer.     

Male breast cancer in Cowden syndrome patients with germline PTEN mutations

Cowden syndrome (CS) (OMIM 158350) is a multiple hamartoma syndrome associated with germline mutations in the PTEN tumour suppressor gene. While CS is characterised most commonly by non-cancerous lesions (mucocutaneous trichilemmomas, acral and palmoplantar keratoses, and papillomatous papules), it is also associated with an increased susceptibility to breast cancer (in females) and thyroid cancer, as well as non-cancerous conditions of the breast and thyroid. Here we report two cases of male breast cancer occurring in patients with classical CS phenotypes and germline PTEN mutations. The first subject was diagnosed with CS indicated primarily by mucocutaneous papillomatosis, facial trichilemmomas, and macrocephaly with frontal bossing at the age of 31 years. He developed breast cancer at 41 years and subsequently died of the disease. A PTEN mutation, c.802delG, was identified in this subject, yet none of his family members showed evidence of a CS phenotype, suggesting that this PTEN mutation may be a de novo occurrence. The second subject had a CS phenotype including multiple trichilemmomas and thyroid adenoma, developed male breast cancer at 43 years, and died of the disease at 57 years. He was a carrier of a PTEN mutation c.347-351delACAAT that cosegregated with the CS phenotype in affected family members. These two cases of male breast cancer associated with germline PTEN mutations and the CS phenotype suggest that CS may be associated with an increased risk of early onset male as well as female breast cancer.     

Male breast cancer: A case of apocrine carcinoma with psammoma bodies

A case of apocrine carcinoma of the breast with psammoma bodies is described in a 69 year old man. The report emphasizes the rarity of this lesion and supports currently held beliefs about the formation of psammoma bodies.     

Male breast cancer: An update in diagnosis,treatment and molecular profiling

Significant advances have been made in the diagnosis and treatment of female breast cancer, resulting in a decline in incidence and a global improvement in clinical outcome. The statistics for male breast cancer (MBC) stand in sharp contrast—over the past several decades, there has been a steady rise in the incidence of this disease, and clinical outcome has improved at a much slower pace. In the current review, the clinicopathologic features of MBC are described in detail. An emphasis is placed on molecular profiling of MBC, which may identify candidate biomarkers and putative targets for pharmacologic intervention. The current role of cytotoxic chemotherapy and endocrine therapy (including tamoxifen, aromatase inhibitors and GnRH analogues) is defined in the context of currently available studies. Furthermore, the potential role of targeted agents, including HER2-directed therapies, PARP inhibitors, and angiogenesis inhibitors, is delineated.     

Male breast carcinoma. An ultrastructural study.

A case of infiltrating ductal carcinoma of the male breast was studied by electron microscopy. The ultrastructure of the tumor is similar to that described in the female breast. Myofibroblasts are the preponderant cells in the stroma. Their significance and possible relation to hormonal stimuli are discussed.     

Amplified in breast cancer 1 expression in breast cancer

Aims: The amplified in breast cancer 1 (AIB1), steroid receptor co‐activator family member, acts as an oestrogen receptor (ER) co‐activator. Acting with HER‐2, it is thought to play a role in endocrine resistance by facilitating ER–growth factor crosstalk. The aim was to analyse AIB1 expression by immunohistochemistry and study its correlations with other prognostic variables in breast cancer and its effect on survival. Methods: A tissue microarray comprising tumours from 438 patients with 15.4 years’ median follow‐up was used. Interpretable AIB1 expression obtained in 395 patients was analysed along with other prognostic factors in breast cancer. Results: AIB1 expression scores ranged from 0 to 30; positive AIB1 expression (score > 14) was seen in 146/395 breast cancers; it correlated negatively with ER (P = 0.003) and progesterone receptor (PR) (P = 0.007), and positively with HER‐2 (P = 0.005) and tumour grade (P = 0.014). It did not correlate with nodal status (P = 0.437). Among ER+ patients, AIB1 expression showed a trend towards loss of PR expression (29% versus 20%; P = 0.14). AIB1 did not predict survival on univariate or multivariate analysis. Conclusions: AIB1 expression correlates with HER‐2 expression in breast cancer and shows a trend of association with loss of PR expression in ER+ tumours. Our study supports the postulated role of AIB1 in ER–growth factor interactions.     

孕酮调节乳腺癌耐药蛋白的机制研究

目的: 探讨孕酮调控乳腺癌耐药蛋白(BCRP)表达的机制。方法: 通过米托蒽醌(MX)诱导或基因转染的方法,作用于孕酮受体(PR)阳性的T47D和PR阴性的MDA-MB-231乳腺癌细胞系,建立由 BCRP 启动子或巨细胞病毒(CMV)启动子启动表达BCRP的4种耐药细胞系T47D/MX、T47D/CMV-BCRP、MDA-MB-231/MX和MDA-MB-231/CMV-BCRP,将孕酮加入耐药细胞的培养液中,通过RT-PCR、Western blotting及MX外排实验观察其对不同耐药细胞系BCRP表达的影响。结果: 孕酮可以剂量依赖方式明显上调PR阳性的乳腺癌细胞系T47D/MX中BCRP mRNA和蛋白的表达,细胞中MX的荧光强度明显减弱。而对照组T47D/CMV-BCRP、MDA-MB-231/MX和MDA-MB-231/CMV-BCRP细胞系,各组处理前后相比,BCRP的表达量无明显变化。结论: 孕酮可能通过PR的介导与 BCRP 启动子上游调控序列中的孕激素反应元件(PRE)结合,激活 BCRP 基因的启动子而增强BCRP mRNA的转录,正性调节BCRP蛋白的表达和功能。