High frequency of skewed X inactivation in young breast cancer patients
High frequency of skewed X inactivation in young breast cancer patients
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DOI：
10.1136/jmg.39.1.30
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发表时间：
2002-01-01
影响因子：
4
通讯作者：
Orstavik, KH
中科院分区：
文献类型：
--
作者：
Kristiansen, M;Langerod, A;Orstavik, KH
简介：最近的研究表明，浸润性卵巢癌患者的外周血细胞中的X染色体失活频率高于边缘性卵巢癌患者和对照组。在这项研究中，我们分析了216例乳腺癌患者外周血中的X染色体失活模式。方法：X染色体失活分析采用Hpall预消化DNA，然后用PCR扩增雄激素受体基因（AR）的高度多态性CAG重复序列，仅扩增未消化的失活X染色体。当90%或更多的细胞优先使用一条X染色体时，X失活模式被归类为偏斜。（27-45岁）有较高的频率偏X失活比年轻的对照（分别为13%和1%）（p=0.009），而中年和老年患者与同龄对照组相比无差异。结论：X连锁肿瘤抑制基因中的生殖系突变可能会使活性X染色体上具有这种突变的细胞具有增殖优势，从而导致X失活偏斜并增加患癌症的风险。另一种可能的解释是，由于X连锁的低等位基因易感性等位基因受失活模式的影响，具有体质偏斜的X失活模式的女性更容易患乳腺癌。
Introduction: Patients with invasive ovarian cancer were recently shown to have a higher frequency of skewed X chromosome inactivation in peripheral blood cells compared to patients with borderline cancer and controls. In this study, we analysed the X inactivation pattern in peripheral blood from 216 breast cancer patients.Methods: X inactivation analysis was performed using Hpall predigestion of DNA followed by PCR of the highly polymorphic CAG repeat of the androgen receptor gene (AR), which amplifies the undigested inactive X chromosome only. The X inactivation pattern was classified as skewed when 90% or more of the cells preferentially used one X chromosome.Results: Young breast cancer patients (27-45 years) had a higher frequency of skewed X inactivation than young controls (13 and 1%, respectively) (p=0.009), whereas no difference was found for middle aged and older patients compared to controls of a similar age.Conclusions: A germline mutation in an X linked tumour suppressor gene may give a proliferative advantage to cells with this mutation on the active X chromosome, thus causing skewed X inactivation and an increased risk for developing cancer. Another possible explanation could be that females with a constitutionally skewed X inactivation pattern are more susceptible to develop breast cancer because of an X linked low penetrance susceptibility allele that is affected by the inactivation pattern.