Variations of BRAF mutant allele percentage in melanomas.
Variations of BRAF mutant allele percentage in melanomas.
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DOI：
10.1186/s12885-015-1515-3
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发表时间：
2015-07-04
期刊：
影响因子：
3.8
通讯作者：
Emile JF
中科院分区：
文献类型：
--
作者：
Hélias-Rodzewicz Z;Funck-Brentano E;Baudoux L;Jung CK;Zimmermann U;Marin C;Clerici T;Le Gall C;Peschaud F;Taly V;Saiag P;Emile JF
BRAF突变存在于40%的人类皮肤黑色素瘤中。BRAF突变等位基因百分比（BRAF-M%）增加的突变肿瘤可能对RAF/MEK抑制剂有更好的反应。我们评估了黑色素瘤的BRAF-M%及其变异的遗传原因。通过焦磷酸测序、实时PCR（rtPCR）和/或皮升液滴PCR（dPCR）定量BRAF-M%。免疫组化法检测BRAF突变体的表达。用荧光原位杂交（FISH）和单核苷酸多态性（SNP）阵列分析染色体改变。焦磷酸测序获得的BRAF-M%定量与rtPCR和dPCR高度相关（R = 0.94）。从DNA和RNA定量的BRAF-M%也高度相关（R = 0.98）。在具有> 80%肿瘤细胞的368个样品中，38.6%具有BRAFV 600 E突变。仅66.2%的病例为杂合子（BRAF-M% 30 - 60%）。在19%的病例中观察到BRAF-M%增加（> 60%）。FISH显示BRAF野生型、杂合型和非杂合型BRAF突变样品中7号染色体的多体性分别为13.6%、35.3%和54.5%（P < 0.005）。BRAF基因座扩增（5.6%）和丢失（3.2%）少见.相比之下，在27/27例BRAF突变痣中，7号染色体为二体。BRAF-M%是异质性的，并且在BRAF突变型黑色素瘤中经常增加。7号染色体的非整倍体在BRAF突变型黑色素瘤中更常见，特别是在BRAF-M%高的黑色素瘤中。本文的在线版本（doi：10.1186/s12885-015-1515-3）包含补充材料，可供授权用户使用。
BRAF mutations are present in 40 % of human skin melanomas. Mutated tumors with an increased percentage of BRAF mutant alleles (BRAF-M%) may have a better response to RAF/MEK inhibitors. We evaluated the BRAF-M% in melanomas, and the genetic causes of its variation. BRAF-M% was quantified by pyrosequencing, real-time PCR (rtPCR) and/or picoliter-droplet PCR (dPCR). BRAF mutant expression was detected by immunohistochemistry. Chromosomal alterations were analyzed with fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) arrays. BRAF-M% quantification obtained with pyrosequencing was highly correlated (R = 0.94) with rtPCR, and with dPCR. BRAF-M% quantified from DNA and RNA were also highly correlated (R = 0.98). Among 368 samples with >80 % tumor cells, 38.6 % had a BRAFV600E mutation. Only 66.2 % cases were heterozygous (BRAF-M% 30 to 60 %). Increased BRAF-M% (>60 %) was observed in 19 % of cases. FISH showed a polysomy of chromosome 7 in 13.6 %, 35.3 % and 54.5 % of BRAF wild-type, heterozygous and non-heterozygous BRAF-mutated samples, respectively (P < 0.005). Amplification (5.6 %) and loss (3.2 %) of BRAF locus were rare. By contrast, chromosome 7 was disomic in 27/27 BRAF-mutated nevi. BRAF-M% is heterogeneous and frequently increased in BRAF-mutant melanomas. Aneuploidy of chromosome 7 is more frequent in BRAF mutant melanomas, specifically in those with high BRAF-M%. The online version of this article (doi:10.1186/s12885-015-1515-3) contains supplementary material, which is available to authorized users.
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