Arlm1 is a male-specific modifier of astrocytoma resistance on mouse Chr 12
Arlm1 is a male-specific modifier of astrocytoma resistance on mouse Chr 12
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DOI：
10.1093/neuonc/nor206
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发表时间：
2012-02-01
期刊：
影响因子：
15.9
通讯作者：
Reilly, Karlyne M.
中科院分区：
文献类型：
--
作者：
Amlin-Van Schaick, Jessica C.;Kim, Sungjin;Reilly, Karlyne M.
虽然许多癌症表现出性别偏见，但性别偏见背后的遗传基础和分子机制并不总是清楚的。星形细胞瘤和胶质母细胞瘤在人类中以男性为主。我们以前已经证明，在NF1-/+；TrP53-/+顺式(NPcis)小鼠模型中形成的胶质瘤在某些遗传背景下也显示出性别偏见。通过跨物种比较，我们已经确定了星形细胞瘤/胶质母细胞瘤的候选男性特异性修饰物。对B6X(B6X129)-NPcis小鼠的连锁分析发现了一种男性特有的星形细胞瘤抗性修饰物，命名为Arlm1，位于小鼠Chr 12的远端。Arm1与人胶质母细胞瘤中改变的人Chr 7p15、7p21、7q36和14q32区域同线。这些基因中的一个子集显示了男性特有的与胶质母细胞瘤患者生存时间的相关性，并代表了Arlm1修饰基因的强有力的候选基因。识别男性特有的修饰基因将有助于更好地理解星形细胞瘤和胶质母细胞瘤中男性占优势的分子基础。
While many cancers show a sex bias, the genetic basis and molecular mechanisms underlying sex bias are not always clear. Astrocytoma and glioblastoma show male predominance in humans. We have shown previously that glial tumors forming in the Nf1-/+; Trp53-/+cis (NPcis) mouse model also show a sex bias in some genetic contexts. Using cross-species comparisons we have identified candidate male-specific modifiers of astrocytoma/glioblastoma. Linkage analysis of B6X(B6X129)-NPcis mice identifies a modifier of astrocytoma resistance specific to males, named Arlm1, on distal mouse Chr 12. Arlm1 is syntenic to human Chr 7p15, 7p21, 7q36, and 14q32 regions that are altered in human glioblastoma. A subset of these genes shows male-specific correlations to glioblastoma patient survival time and represents strong candidates for the Arlm1 modifier gene. Identification of male-specific modifier genes will lead to a better understanding of the molecular basis of male predominance in astrocytoma and glioblastoma.