Aberrant methylation of imprinted genes is associated with negative hormone receptor status in invasive breast cancer.
Aberrant methylation of imprinted genes is associated with negative hormone receptor status in invasive breast cancer.
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DOI：
10.1002/ijc.29419
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发表时间：
2015-08-01
影响因子：
6.4
通讯作者：
Michels, Karin B.
中科院分区：
文献类型：
--
作者：
Barrow, Timothy M.;Barault, Ludovic;Ellsworth, Rachel E.;Harris, Holly R.;Binder, Alexandra M.;Valente, Allyson L.;Shriver, Craig D.;Michels, Karin B.
印迹基因的表观遗传调控使单等位基因表达根据父母的起源，它的破坏是牵连在许多癌症和发育障碍。激素受体的表达在乳腺癌中具有重要意义，因为它们是癌细胞生长速率的指标，并决定对内分泌治疗的反应。我们调查了侵袭性乳腺癌中9个印记位点的DNA甲基化异常事件和变异的频率，并检查了与雌激素和孕激素受体状态的相关性。将浸润性乳腺癌（n=38）和良性乳腺疾病（n=30）患者的乳腺组织和血液与健康个体（n=36）的乳腺组织和血液进行比较，根据诊断时的年龄、种族、BMI、绝经状态和癌症家族史与癌症患者匹配。焦磷酸测序分析DNA甲基化和等位基因特异性表达。在59%的癌症患者中观察到IGF 2 DMR 2的肿瘤特异性甲基化变化，IGF 2 DMR 0为38%，DIRAS 3 DMR为36%，GRB 10 ICR为23%，PEG 3 DMR为21%，MEST ICR为19%，H19 ICR为18%，KvDMR为8%，SNRPN/SNURF ICR为4%。癌症患者乳腺组织中甲基化的变化显著大于健康个体和良性乳腺疾病。三个或更多位点的异常甲基化与阴性雌激素-α（Fisher精确检验，p=0.02）和孕酮-A（p=0.02）受体状态显著相关。因此，印迹基因DNA甲基化的异常事件和增加的变化似乎在浸润性乳腺癌中是常见的，并且与阴性雌激素和孕激素受体状态相关，而不丧失单等位基因表达。
Epigenetic regulation of imprinted genes enables monoallelic expression according to parental origin, and its disruption is implicated in many cancers and developmental disorders. The expression of hormone receptors is significant in breast cancer as they are indicators of cancer cell growth rate and determine response to endocrine therapies. We investigated the frequency of aberrant events and variation in DNA methylation at nine imprinted sites in invasive breast cancer and examined the association with estrogen and progesterone receptor status. Breast tissue and blood from patients with invasive breast cancer (n=38) and benign breast disease (n=30) were compared to those from healthy individuals (n=36), matched to the cancer patients by age at diagnosis, ethnicity, BMI, menopausal status, and familial history of cancer. DNA methylation and allele-specific expression were analyzed by pyrosequencing. Tumor-specific methylation changes at IGF2 DMR2 were observed in 59% of cancer patients, IGF2 DMR0 in 38%, DIRAS3 DMR in 36%, GRB10 ICR in 23%, PEG3 DMR in 21%, MEST ICR in 19%, H19 ICR in 18%, KvDMR in 8%, and SNRPN/SNURF ICR in 4%. Variation of methylation was significantly greater in breast tissue from cancer patients than healthy individuals and benign breast disease. Aberrant methylation of three or more sites was significantly associated with negative estrogen-alpha (Fisher’s Exact Test, p=0.02) and progesterone-A (p=0.02) receptor status. Aberrant events and increased variation of imprinted gene DNA methylation therefore appear to be frequent in invasive breast cancer and are associated with negative estrogen and progesterone receptor status, without loss of monoallelic expression.
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影响因子：
11.2
作者：
Fackler MJ;Umbricht CB;Williams D;Argani P;Cruz LA;Merino VF;Teo WW;Zhang Z;Huang P;Visvananthan K;Marks J;Ethier S;Gray JW;Wolff AC;Cope LM;Sukumar S
通讯作者：
Sukumar S
影响因子：
3.7
作者：
Barbaux S;Gascoin-Lachambre G;Buffat C;Monnier P;Mondon F;Tonanny MB;Pinard A;Auer J;Bessières B;Barlier A;Jacques S;Simeoni U;Dandolo L;Letourneur F;Jammes H;Vaiman D
通讯作者：
Vaiman D
影响因子：
4.7
作者：
Chik, Flora;Machnes, Ziv;Szyf, Moshe
通讯作者：
Szyf, Moshe
影响因子：
4.8
作者：
Dalai, Irene;Missiaglia, Edoardo;Scarpa, Aldo
通讯作者：
Scarpa, Aldo
影响因子：
56.9
作者：
Cui, HM;Cruz-Correa, M;Feinberg, AP
通讯作者：
Feinberg, AP