CXCR4 pathway associated with family history of melanoma.
CXCR4 pathway associated with family history of melanoma.
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CXCR4 通路与黑色素瘤家族史相关。
DOI：
10.1007/s10552-013-0315-9
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Qureshi,AbrarA
中科院分区：
文献类型：
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作者：
Li,Wen-Qing;Han,Jiali;Widlund,HansR;Correll,Mick;Wang,YaoyuE;Quackenbush,John;Mihm,MartinC;Canales,AlvaroLaga;Wu,Shaowei;Golub,Todd;Hoshida,Yujin;Hunter,DavidJ;Murphy,George;Kupper,ThomasS;Qureshi,AbrarA
目的遗传易感性在黑色素瘤的病因中起主要作用，但已知的遗传标记只占家族史相关黑色素瘤病例的一小部分。表达微阵列提供了进一步鉴定与黑色素瘤家族史相关的基因组图谱的机会。我们的目的是区分有和没有黑色素瘤家族史的黑色素瘤患者的mRNA表达特征。方法根据护士健康研究，家族史被定义为有一个或多个被诊断为黑色素瘤的一级家族成员。黑色素瘤的诊断通过回顾病理报告得到确认，肿瘤块是通过邮寄从美国各地收集的。基因组询问是通过在6K或全基因组(24K)Illumina基因芯片上评估78例原发性皮肤侵袭性黑色素瘤福尔马林固定的石蜡包埋组织的表达谱来完成的。结果CXC趋化因子受体4(CXCR4)通路在两个平台的家族性黑色素瘤中持续上调。前沿分析表明，CXCR4途径中的4个基因，包括MAPK1、PLCG1、CRK和PTK2，是导致该途径丰富的核心成员。CXCR4通路的丰富与NRAS、BRAF突变或Breslow厚度无关。结论CXCR4通路可能构成一种新的与黑色素瘤家族史相关的易感通路。
PurposeGenetic predisposition plays a major role in the etiology of melanoma, but known genetic markers only account for a limited fraction of family-history-associated melanoma cases. Expression microarrays have offered the opportunity to identify further genomic profiles correlated with family history of melanoma. We aimed to distinguish mRNA expression signatures between melanoma cases with and without a family history of melanoma.MethodsBased on the Nurses’ Health Study, family history was defined as having one or more first-degree family members diagnosed with melanoma. Melanoma diagnosis was confirmed by reviewing pathology reports, and tumor blocks were collected by mail from across the USA. Genomic interrogation was accomplished through evaluating expression profiling of formalin-fixed paraffin-embedded tissues from 78 primary cutaneous invasive melanoma cases, on either a 6K or whole-genome (24K) Illumina gene chip. Gene set enrichment analysis was performed for each batch to determine the differentially enriched pathways and key contributing genes.ResultsThe CXC chemokine receptor 4 (CXCR4) pathway was consistently up-regulated within cases of familial melanoma in both platforms. Leading edge analysis showed four genes from the CXCR4 pathway, includingMAPK1,PLCG1,CRK, andPTK2, were among the core members that contributed to the enrichment of this pathway. There was no association between the enrichment of CXCR4 pathway andNRAS,BRAFmutation, or Breslow thickness of the primary melanoma cases.ConclusionsWe found that the CXCR4 pathway might constitute a novel susceptibility pathway associated with family history of melanoma in first-degree relatives.