Saed G M, Ladin D, Olson J, Han X, Hou Z, Fivenson D
Department of Dermatology, Henry Ford Hospital, Detroit, Mich., USA.
Arch Dermatol. 1998 Aug;134(8):963-7. doi: 10.1001/archderm.134.8.963.
Keloids are the result of a dysregulated wound healing process. They are characterized by the formation of excess scar tissue that proliferates beyond the boundaries of the original wound. Somatic mutations of p53 have been implicated as causal events in up to 50% of all human malignancies. In addition, p53 has been shown to play an important role in controlling cell proliferation and apoptosis. We hypothesize that mutations in p53 can lead to a hyperproliferative state that can result in keloid formation.
To detect p53 DNA mutations in tissues and cultured fibroblasts from skin lesions of 7 patients with keloids.
The polymerase chain reaction followed by single-strand conformational polymorphism analysis and direct DNA sequencing were used to detect p53 gene mutations.
The Department of Dermatology, Henry Ford Hospital, Detroit, Mich.
Seven patients with keloids seen for routine surgical excision of their lesions. Normal DNA specimens were obtained from buccal smears and healthy skin samples from these patients.
Mutations in the p53 were identified in all patients by polymerase chain reaction followed by single-strand conformational polymorphism analysis and subsequently confirmed by DNA sequencing. A mutation in exon 5 resulting in amino acid substitution was found in 1 of the patients in keloid tissue and cultured keloid fibroblasts (codon 156, CGC-->CCC, arginine-->proline). Frameshift mutations in exons 5 and 6 caused by the insertion or deletion of a nucleotide at different positions were found in 6 patients with keloids in both keloid tissues and cultured fibroblasts. Mutations in exon 4 resulting in amino acid substitution were found in all patients in both keloid tissues and cultured fibroblasts (all in codon 72, CGC-->CCC, arginine-->proline). No p53 mutations were detected in buccal smears or cultured fibroblasts from healthy skin samples of any of the patients.
Focal mutations in p53 may increase cell proliferation and decrease cell death in the dysregulated growth patterns that have been clinically documented. An understanding of the pattern of all growth dysregulation related to keloids may lead to new therapeutic strategies.
瘢痕疙瘩是伤口愈合过程失调的结果。其特征是形成超出原始伤口边界增生的过多瘢痕组织。p53的体细胞突变被认为是高达50%的人类恶性肿瘤的致病因素。此外，p53已被证明在控制细胞增殖和凋亡中起重要作用。我们推测p53突变可导致细胞过度增殖状态，进而导致瘢痕疙瘩形成。
检测7例瘢痕疙瘩患者皮肤病变组织及培养的成纤维细胞中的p53 DNA突变。
采用聚合酶链反应，随后进行单链构象多态性分析和直接DNA测序来检测p53基因突变。
密歇根州底特律市亨利·福特医院皮肤科。
7例因瘢痕疙瘩病变接受常规手术切除的患者。从这些患者的口腔涂片和健康皮肤样本中获取正常DNA标本。
通过聚合酶链反应，随后进行单链构象多态性分析，在所有患者中均鉴定出p53突变，随后通过DNA测序得以证实。1例患者的瘢痕疙瘩组织及培养的瘢痕疙瘩成纤维细胞中发现外显子5发生突变，导致氨基酸替换（密码子156，CGC→CCC，精氨酸→脯氨酸）。6例瘢痕疙瘩患者的瘢痕疙瘩组织及培养的成纤维细胞中均发现外显子5和6因不同位置核苷酸的插入或缺失导致的移码突变。所有患者的瘢痕疙瘩组织及培养的成纤维细胞中均发现外显子4发生导致氨基酸替换的突变（均在密码子72，CGC→CCC，精氨酸→脯氨酸）。在任何患者的口腔涂片或健康皮肤样本培养的成纤维细胞中均未检测到p53突变。
p53的局灶性突变可能在临床上已记录的失调生长模式中增加细胞增殖并减少细胞死亡。了解与瘢痕疙瘩相关的所有生长失调模式可能会带来新的治疗策略。
