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恶性黑色素瘤和先天性痣中N-ras癌基因的点突变。

Point mutations in the N-ras oncogene in malignant melanoma and congenital naevi.

作者信息

Carr J, Mackie R M

机构信息

Department of Dermatology, University of Glasgow, U.K.

出版信息

Br J Dermatol. 1994 Jul;131(1):72-7. doi: 10.1111/j.1365-2133.1994.tb08460.x.

DOI:10.1111/j.1365-2133.1994.tb08460.x
PMID:8043423
Abstract

DNA from formalin-fixed and paraffin-processed samples from 100 melanocytic lesions (39 malignant melanomas, 18 cases of dysplastic naevi, and 43 congenital naevi) was extracted, and the sequences around codons 12/13 and 61 of the N-ras oncogene were amplified using the polymerase chain reaction. The amplified product was then analysed both by dot-blotting and by direct sequencing for point mutations. By the dot-blotting technique, mutations were seen in 18 of 100 lesions. These were in one of five distant metastases (20%), in one of three nodal metastases (33%), in four of 31 (13%) primary melanomas, in none of 18 dysplastic naevi, and in 12 of 43 (28%) congenital naevi, all at codon 61. On direct sequencing, nine of 18 mutations were confirmed, in two of 31 (6%) primary tumours, one distant metastasis, and six of 43 (14%) congenital naevi. Of the 23 superficial spreading melanomas examined, eight were on sun-exposed skin. A superficial spreading melanoma, in which the N-ras mutation at codon 61 was confirmed, was on non-exposed skin, and an unconfirmed mutation was from an exposed site. One of three nodular melanomas with a confirmed mutation was on a light-exposed site, and the other two nodular melanomas were from non-exposed areas. All four lentigo maligna melanomas were from exposed sites, and one of these had an unconfirmed mutation. The only acral lentiginous melanoma, which had no mutation, was from a sun-exposed area.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

从100例黑素细胞性病变(39例恶性黑素瘤、18例发育异常痣和43例先天性痣)的福尔马林固定石蜡包埋样本中提取DNA,采用聚合酶链反应扩增N-ras癌基因第12/13密码子和第61密码子周围的序列。然后通过斑点杂交和直接测序分析扩增产物的点突变。通过斑点杂交技术,在100个病变中有18个发现突变。这些突变见于5个远处转移灶中的1个(20%)、3个淋巴结转移灶中的1个(33%)、31个原发性黑素瘤中的4个(13%)、18个发育异常痣中无、43个先天性痣中的12个(28%),均位于第61密码子。直接测序证实18个突变中的9个,见于31个原发性肿瘤中的2个(6%)、1个远处转移灶和43个先天性痣中的6个(14%)。在检查的23例浅表扩散性黑素瘤中,8例位于阳光暴露皮肤。1例经证实第61密码子N-ras突变的浅表扩散性黑素瘤位于非暴露皮肤,1例未证实的突变来自暴露部位。3例经证实有突变的结节性黑素瘤中有1例位于轻度暴露部位,另外2例结节性黑素瘤来自非暴露区域。所有4例恶性雀斑样痣黑素瘤均来自暴露部位,其中1例有未证实的突变。唯一1例无突变的肢端雀斑样痣黑素瘤来自阳光暴露区域。(摘要截短至250字)

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