A melanoma subtype: uveal melanoma.
A melanoma subtype: uveal melanoma.
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黑色素瘤亚型：葡萄膜黑色素瘤。
DOI：
10.1016/j.jaad.2010.06.004
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发表时间：
2011
影响因子：
13.8
通讯作者：
Celebi,JulideTok
中科院分区：
文献类型：
--
作者：
Wu,Julia;Brunner,Georg;Celebi,JulideTok
黑色素瘤是由不同亚群组成的异质性癌症。葡萄膜黑色素瘤是一种独特的亚型，与皮肤黑色素瘤在临床、生物学和遗传学上存在差异。1它起源于虹膜、睫状体或脉络膜的黑素细胞，后者是最常见的位置。诱发因素包括葡萄膜痣和太田痣。它是一种侵袭性肿瘤，大约一半的患者会导致转移。由于血行播散，转移部位是肝脏。与皮肤黑色素瘤相反，由于眼内淋巴引流的缺乏，淋巴播散不会发生。肿瘤的细胞遗传学异常（染色体畸变）和基因表达谱与皮肤黑色素瘤不同。1肿瘤内3号单体和染色体8 q的获得与转移表型相关，而染色体6p的获得发生在低转移风险的肿瘤中。类似地，基因表达特征准确区分低转移性和高转移性风险的肿瘤。1在葡萄膜黑色素瘤中观察到的体细胞遗传改变与皮肤黑色素瘤相比显示出差异。BRAF（40-50%）或NRAS（15-25%）的功能获得性突变在躯干和四肢的皮肤黑色素瘤中很常见。2肢端黑色素瘤中存在基因剂量增加或KIT突变（39%）。3 BRAF、NRAS、KIT突变在葡萄膜黑色素瘤中极为罕见。4这些遗传改变导致RAS-ERK通路的激活，该通路对于增殖、存活、迁移和分化信号至关重要，并且在大多数黑色素瘤中几乎被激活。最近，在葡萄膜黑色素瘤（83%）以及其他黑色素细胞肿瘤中已经报道了导致RAS-ERK激活的GNAQ基因的功能获得性突变（总结在表1中）。5-8 GNAQ的突变谱尚未在皮肤黑色素瘤的大队列中得到验证。在此，我们报告了一组皮肤黑色素瘤（n= 122）中GNAQ基因（外显子5）热点区域的测序，该组皮肤黑色素瘤包括躯干和四肢黑色素瘤（n= 83），肢端黑色素瘤（n= 25）和未知部位黑色素瘤（n= 14）。由于与GNAQ的序列同源性，还测试了GNA 11基因中的突变。在53例（44%）和23例（19%）病例中发现BRAF突变和NRAS突变，但未发现GNAQ或GNA 11突变。这项研究证实了最近的研究结果，GNAQ的体细胞突变是罕见的，如果有的话，在黑色素瘤，从表皮黑色素细胞的躯干，四肢和肢端网站。
Melanoma is a heterogeneous cancer consisting of different subsets. Uveal melanoma is a distinct subtype with clinical, biologic, and genetic differences from cutaneous melanoma. 1 It arises from melanocytes of the iris, ciliary body or the choroid, the latter being the most common location. Predisposing factors include uveal nevus and nevus of Ota. It is an aggressive tumor with approximately half of patients resulting in metastasis. The site of metastasis is the liver due to hematogenous spread. In contrast to cutaneous melanoma, lymphatic dissemination does not occur due to an absence of lymphatic drainage of the ocular interior. The cytogenetic abnormalities (chromosomal aberrations) of the tumor and gene expression profiles are different from cutaneous melanoma. 1 Monosomy 3 and gain of chromosome 8q within the tumor associate with a metastatic phenotype whereas gain of chromosome 6p occurs in tumors with low metastatic risk. Similarly, gene expression signatures accurately distinguish tumors at low metastatic and high metastatic risk. 1 Somatic genetic alterations observed in uveal melanoma show differences compared to cutaneous melanoma. Gain-of-function mutations in BRAF (40-50%) or NRAS (15-25%) are common among cutaneous melanomas of the trunk and extremities. 2 Increase gene dosage or mutations of KIT (39%) are observed among acral melanomas. 3 BRAF, NRAS, KIT mutations are extremely rare in uveal melanoma. 4 These genetic alterations lead to activation of the RAS-ERK pathway that is critical for proliferation, survival, migration, and differentiation signals and is virtually activated in the majority of melanomas.Recently, gain-of-function mutations in the GNAQ gene that leads to RAS-ERK activation have been reported in uveal melanoma (83%) as well as in other melanocytic tumors (summarized in Table 1). 5-8 The mutational profile of GNAQ has not been validated in large cohorts of cutaneous melanoma. Here, we report sequencing of the hotspot regions of the GNAQ gene (exon 5) as described previously5 in a cohort of cutaneous melanomas (n= 122) consisting of melanomas of the trunk and extremities (n= 83), acral sites (n= 25), and unknown sites (n= 14). Due to sequence homology to GNAQ, mutations in GNA11 gene were also tested. BRAF mutations were found in 53 (44%) and NRAS in 23 cases (19%), however no mutations in GNAQ or GNA11 were identified. This study validates recent findings that somatic mutations in GNAQ are rare, if any, among melanomas that arise from epidermal melanocytes of the trunk, extremities and acral sites.
DOI：
10.2217/14796694.4.5.629
发表时间：
2008-10
期刊：
Future oncology (London, England)
影响因子：
--
作者：
Landreville S;Agapova OA;Harbour JW
通讯作者：
Harbour JW
影响因子：
45.3
作者：
Curtin, John A.;Busam, Klaus;Bastian, Boris C.
通讯作者：
Bastian, Boris C.
影响因子：
6.4
作者：
Saldanha, G;Purnell, D;Pringle, JH
通讯作者：
Pringle, JH