Correlation of Global MicroRNA Expression With Basal Cell Carcinoma Subtype

被引:32
作者
Heffelfinger, Christopher [2 ]
Ouyang, Zhengqing [3 ,4 ,5 ]
Engberg, Anna [6 ]
Leffell, David J. [7 ]
Hanlon, Allison M. [6 ]
Gordon, Patricia B. [1 ]
Zheng, Wei [8 ]
Zhao, Hongyu [9 ]
Snyder, Michael P. [3 ]
Bale, Allen E. [1 ,7 ]
机构
[1] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
[2] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA
[3] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
[4] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA
[5] Stanford Univ, Program Epithelial Biol, Stanford, CA 94305 USA
[6] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA
[7] Yale Comprehens Canc Ctr, New Haven, CT USA
[8] Yale Univ, Keck Lab, New Haven, CT 06520 USA
[9] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
SKIN-CANCER; DIFFERENTIAL EXPRESSION; HISTOLOGIC EVOLUTION; GENE; MUTATIONS; MIGRATION; PROFILES; SUNLIGHT; GROWTH; PCR;
D O I
10.1534/g3.111.001115
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Basal cell carcinomas (BCCs) are the most common cancers in the United States. The histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior. In this study, global miRNA expression was quantified by high-throughput sequencing in nodular BCCs, a subtype that is slow growing, and infiltrative BCCs, aggressive tumors that extend through the dermis and invade structures such as cutaneous nerves. Principal components analysis correctly classified seven of eight infiltrative tumors on the basis of miRNA expression. The remaining tumor, on pathology review, contained a mixture of nodular and infiltrative elements. Nodular tumors did not cluster tightly, likely reflecting broader histopathologic diversity in this class, but trended toward forming a group separate from infiltrative BCCs. Quantitative polymerase chain reaction assays were developed for six of the miRNAs that showed significant differences between the BCC subtypes, and five of these six were validated in a replication set of four infiltrative and three nodular tumors. The expression level of miR-183, a miRNA that inhibits invasion and metastasis in several types of malignancies, was consistently lower in infiltrative than nodular tumors and could be one element underlying the difference in invasiveness. These results represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene expression may be involved in tumor pathogenesis and particularly in determining the aggressiveness of these malignancies.
引用
收藏
页码:279 / 286
页数:8
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