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1.
目的:明确先天性色素痣(congenital melanocytic nevi, CMN)中BRAF(V600E)基因突变对其增殖活性和组织病理学的影响。方法:回顾分析2018年12月至2020年12月我院皮肤科诊治的185例CMN患儿,所有患儿均进行基因检测、病理检查和Ki67免疫组化检测。根据基因检测结果是否存在BRAFV600E突变,将入选患儿分为突变组和对照组,然后再根据性别、年龄、皮损大小和皮损部位进行配对后进一步研究。结果:突变组Ki67指数、痣细胞累及深度、痣细胞巢个数、痣细胞巢大小与对照组比较差异均有统计学意义(均P<0.05)。与BRAF V600E阴性的CMN相比,BRAF(V600E)阳性CMN通常在表真皮交界部位形成黑素细胞巢,且巢较大。痣细胞累及深度和痣细胞巢个数与Ki67指数之间成正相关(均P<0.05)。结论:BRAF(V600E)基因突变使CMN的增殖活性明显升高,并对其组织病理学有特殊的影响。  相似文献   

2.
BRAF mutations have recently been detected with a high frequency (66%) in cutaneous melanoma. All those mutations are activating, with a single substitution (T1796A) at codon 599 (V599E) accounting for over 90%. To investigate the stage in which those mutations occur in the currently proposed sequential malignant transformation of melanocytes, 22 benign melanocytic nevi, 23 melanocytic atypical nevi, and 25 primary cutaneous melanoma from 63 different patients were examined for BRAF mutations using DNA extracted from microdissected formalin-fixed and paraffin-embedded tissues, and a two-round PCR-RFLP-based strategy. A subset of samples was sequenced for mutation confirmation. Sixteen benign (73%) and eleven atypical (52%) melanocytic nevi, and thirteen melanoma (56%) demonstrated BRAF mutations at codon 599, and no statistically significant differences were detected among all three types of lesions. No mutations were demonstrated in microdissected epidermal keratinocytes adjacent to melanocytic lesions having BRAF mutations. No correlation was detected between BRAF mutational status and age, sun exposure, and Clark's level in malignant melanoma. However, comparing only atypical nevi and melanoma lesions the frequency of BRAF mutation is significantly greater in male (78%) than female (35%) patients (P = 0.0194). The previously described T1796A point mutation was detected in 17 of 18 mutated samples, and a novel mutation consisting of a substitution of valine for lysine (GT1795-96AA) was detected in one melanoma case. Our findings of a high frequency of BRAF mutations at codon 599 in benign melanocytic lesions of the skin indicate that this mutation is not sufficient by itself for malignant transformation.  相似文献   

3.
BackgroundA lot of congenital melanocytic nevi (CMN) carry the somatic mutation in the oncogene BRAF V600E. But the detailed histopathologic characteristics and the proliferative activity of CMN with BRAF V600E gene mutation have not been systematically documented.ObjectiveTo identify the proliferative activity and histopathological features correlating them with BRAF V600E gene mutation status in CMN.MethodsCMN were retrospectively identified from the laboratory reporting system. Mutations were determined by Sanger sequencing. The CMN were divided into a mutant group and control group according to whether there was BRAF gene mutation and were strictly matched according to gender, age, nevus size, and location. Histopathological analysis, analysis of Ki67 expression by immunohistochemistry and laser confocal fluorescence microscopy were performed.ResultsThe differences in Ki67 index, the depth of nevus cell involvement and the number of nevus cell nests between the mutant group and the control group was statistically significant, with p-values of 0.041, 0.002 and 0.007, respectively. Compared with BRAF V600E negative nevi, BRAF V600E positive nevi often exhibited predominantly nested intraepidermal melanocytes, and larger junctional nests, but the difference in this data sets were not statistically significant. The number of nests (p = 0.001) was positively correlated with the proportion of Ki67 positive cells.Study limitationsA small sample of patients were included and there was no follow-up.ConclusionsBRAF V600E gene mutations were associated with high proliferative activity and distinct histopathological features in congenital melanocytic nevi.  相似文献   

4.
Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample was typed for 16 single nucleotide polymorphisms (SNP) within the BRAF gene, and five SNP in three neighboring genes. The sample comprised 755 melanoma cases from 740 families stratified by family history of melanoma and controls from 635 unselected twin families (2,239 individuals). Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling, and pigmentation phenotype. Genotyping was carried out via primer extension followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. SNP in the BRAF gene were found to be weakly associated with melanoma status but not with development of nevi or freckles. The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6%. This study shows that BRAF polymorphisms predispose to melanoma but the causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of 0.2%.  相似文献   

5.
Phenotypic characteristics of members of a melanoma prone kindred with a V126D CDKN2A gene mutation were monitored over approximately 15 y. Thirty-eight previously studied subjects were recruited. Participants underwent a complete skin examination by the same dermatologist who examined them initially. The size and location of all nevi were recorded on a body map diagram. Total nevus number (TNN) and total nevus density (TND) were determined. CDKN2A sequencing verified 13 mutation carriers and 16 non-carriers. Nine participants were spouse controls without a history of melanoma and did not carry a CDKN2A mutation. Mutation carriers demonstrated a greater mean TNN and TND at initial and follow-up examinations compared with non-carriers and continued to develop nevi rather than show nevus regression seen in non-carriers and spouse controls. Non-carriers showed an intermediate nevus phenotype between mutation carriers and spouse controls. Four of the 13 mutation carriers and one non-carrier have developed invasive melanoma. Over a 15-y interval, TNN and TND were increased in mutation carriers compared with non-carriers and spouse controls. Continued accumulation of nevi in mutation carriers supports a nevogenic role for this CDKN2A mutation. An intermediate nevus phenotype in non-carrier family members suggests the presence of additional modifier genes.  相似文献   

6.
To investigate whether the frequency of the BRAF(V600E) (V-raf murine sarcoma virus oncogene homolog B1) mutation in melanocytic nevi is associated with sun exposure patterns, we examined 120 acquired melanocytic nevi excised from various anatomic sites, including glabrous skin, as well as 62 congenital nevi. We used a new mutation detection system based on the shifted termination assay, called Mutector, which was able to detect only 5% of heterozygous mutant cells within the samples. We detected the mutation in 105/120 (87.5%) acquired nevi and 43/62 (69.4%) congenital nevi. Notably, we found the mutation in 35/43 (81.4%) acquired nevi excised from glabrous skin and genitalia. These results strongly suggest that UV light is not necessarily required for the acquisition of the BRAF(V600E) mutation, and suggest that non-mutagenic effects of UV light to melanocytes may be more important in the nevogenesis. Additionally, we showed heterogeneous distribution of BRAF-mutated cells within the lesions of small congenital nevi by a combination of laser microdissection and direct sequencing. Finally, we found low frequency of BRAF(V600E) mutation (6/20, 30.0%) in medium-sized congenital nevi. Most of these nevi with wild-type BRAF had neroblastoma ras viral oncogene homolog mutations (9/14, 64.3%), suggesting different pathogenesis of medium-sized congenital nevi from acquired nevi and small congenital nevi.  相似文献   

7.
BRAF kinase gene V599E mutation in growing melanocytic lesions   总被引:1,自引:0,他引:1  
Mutations in the BRAF-gene are found in benign and malignant melanocytic lesions, >90% being a V599E mutation. This mutation results in constitutively active kinase function and increased colony formation in vitro. The biological impact of this mutation in vivo is still debated. To address this question, we used our digital epiluminescence image archive and retrospectively selected 49 melanocytic lesions, which did not meet the criteria of melanoma at the initial presentation. Mean 12 months later these lesions were excised because of increased size or changed structure and BRAF(V599E) mutations were analyzed. Among 36 growing lesions, BRAF(V599E) mutations were found in 16 (11 melanomas and 5 nevi). Among 13 lesions with structural changes, BRAF(V599E) mutations were found in 4 (3 melanomas and 1 nevus). Thirty-five randomly selected additional lesions with no changes during follow-up served as controls, all nevi by histology, and two of them showed a BRAF(V599E) mutation. Statistics revealed odds for the presence of the BRAF(V599E) mutation being seven times higher in lesions with structural changes and 13 times higher in growing lesions as compared with lesions without changes. This raises the question if the V599E mutation determines lesions at risk developing into melanoma and if not, what are the mechanisms controlling growth stop in benign lesions?  相似文献   

8.
OBJECTIVE: To determine the frequency at which the CDKN2A coding region is mutated in the atypical nevi of persons with sporadic melanoma. DESIGN: DNA samples, isolated by laser-captured microdissection of atypical nevi from 10 patients with newly incident cases of sporadic melanoma and their spouses as matched controls, were used as templates for nested polymerase chain reaction amplification of CDKN2A exons 1 and 2. RESULTS: No point mutations in the coding region of CDKN2A were observed in any of the melanocytic nevi. CONCLUSIONS: Point mutations in CDKN2A are an uncommon event in the atypical nevi of persons with melanoma. As such, the data may support a hypothesis of melanocytic nevus histogenesis, in which the melanocytic nevus and malignant melanoma represent separate, pleiotropic pathways resulting from common stimuli, such as genomic damage from UV radiation.  相似文献   

9.
Mutations of the BRAF gene in benign and malignant melanocytic lesions   总被引:6,自引:0,他引:6  
A single-point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage in cultured melanoma cells and in 6 of 9 primary melanomas examined. To evaluate the impact of the T1796A BRAF mutation, we screened primary melanomas, various types of nevi and lesions where a melanoma developed in an underlying nevus. We could detect the mutation in 28 of 97 (29%) melanomas and in 39 of 187 (21%) nevi, including blue nevi (0/20) and Spitz nevi (0/69), which did not carry the mutation. In melanomas with an underlying nevus, either the mutation was present in both the laser-microdissected nevus cells and the laser-microdissected melanoma cells (3/14) or both lesions were negative for the BRAF mutation except one case. In conclusion, mutations in exon 15 of the BRAF gene are nonspecific for progression of a nevus to a melanoma. Other so far unknown cofactors seem to be of importance.  相似文献   

10.
Giant congenital melanocytic nevi (CMNs) are at an increased risk for malignant transformation. To explore the mutation frequencies of BRAF(V600E) (V-raf murine sarcoma virus oncogene homolog B1) and NRAS (neuroblastoma ras viral oncogene homolog) codon 61 in CMNs of Chinese, we selected 55 paraffin-embedded tissue blocks, including 37 cases of medium CMNs (1.5-20cm) and 18 cases of giant CMNs (>20 cm). Direct sequencing was performed to detect the BRAF(V600E) and NRAS codon 61 mutations. The BRAF(V600E) mutations were detected in 9 of 55 nevi (16.4%). In medium CMNs, 9 of 37 BRAF(V600E) mutations (24.3%) were detected. Notably, in giant CMNs, no BRAF(V600E) mutations were found. The difference between these frequencies is statistically significant (P = 0.0231). NRAS codon 61 mutations were detected in 13 of 55 nevi (23.6%), including 10 of 37 medium CMNs (27.0%) and 3 of 18 giant CMNs (16.7%). Additionally, the BRAF(V600E) and NRAS codon 61 mutations did not coexist in the same sample. Finally, we found that the NRAS codon 61 mutation was significantly related to the amount of sun exposure (0 of 18 CMNs from sites of intermittent sun exposure and 13 of 36 CMNs from sites of chronic continuous sun exposure, P = 0.0024). The paradoxically higher incidence of BRAF(V600E) mutations in medium-sized compared with giant CMNs suggests that the presence of the BRAF(V600E) mutation may play different roles between medium and giant CMNs in melanocytic tumorigenesis.  相似文献   

11.
Most melanocytic nevi develop on sun-exposed skin during childhood and adolescence and commonly harbor BRAF mutations or, less frequently, NRAS mutations. A small subset of nevi is present at birth, and therefore must develop independently of UV light. To assess whether these nevi have a different mutation spectrum than those that develop on sun-exposed skin, we determined the BRAF and NRAS mutation frequencies in 32 truly congenital nevi. We found no BRAF mutations, but 81% (26/32) harbored mutations in NRAS. Consistently, seven of 10 (70%) proliferating nodules that developed early in life in congenital nevi showed mutations in NRAS. A separate set of nevi that displayed histological features frequently found in nevi present at birth ("congenital pattern nevi") but lacked a definitive history of presence at birth showed an inverse mutation pattern with common BRAF mutations (20/28 or 71%) and less frequent NRAS mutations (7/28 or 25%). Thus, nevi that develop in utero are genetically distinct from those that develop later, and histopathologic criteria alone are unable to reliably distinguish the two groups. The results are consistent with the finding in melanoma that BRAF mutations are uncommon in neoplasms that develop in the absence of sun-exposure.  相似文献   

12.
The T1796A mutation of the BRAF gene is absent in Spitz nevi   总被引:2,自引:0,他引:2  
BACKGROUND: BRAF, a serine/threonine kinase, is a component of the retrovirus-associated sequence (RAS)-RAF-extracellular-regulated protein kinase (ERK)-MAP kinase signal transduction pathway mediating signals from RAS to ERK. The T1796A single point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage of malignant melanomas and benign melanocytic lesions such as congenital nevi, compound nevi, intradermal nevi and dysplastic nevi. The T1796A mutation has been shown to promote cell proliferation. METHODS: We screened 21 Spitz nevi and six spitzoid malignant melanomas for the presence of the T1796A BRAF mutation. RESULTS: The T1796A BRAF mutation could not be detected in any of the 21 Spitz nevi but was present in two of the six spitzoid malignant melanomas. CONCLUSIONS: Our results, in conjunction with data from a previous investigation, suggest that the melanocytic proliferation of Spitz nevi might be induced by components of the RAS-RAF-ERK-MAP kinase pathway different from BRAF, possibly combined with other genetic aberrations. The lack of the T1796A BRAF mutation might be of practical importance in distinguishing Spitz nevi from other melanocytic lesions simulating Spitz nevi as a part of a future complex diagnostic assay.  相似文献   

13.
Melanocytic lesions, including Spitz nevi (SN), common benign nevi (CBN) and cutaneous metastatic melanoma (CMM), were analyzed for activating mutations in NRAS, HRAS and BRAF oncogenes, which induce cellular proliferation via the MAP kinase pathway. One of 22 (4.5%) SN tested showed an HRAS G61L mutation. Another lesion, a 'halo' SN, showed a BRAF V600E (T1796A) mutation. BRAF V600E mutations were found in two thirds (20/31) of CBN, while a further 19% (6/31) showed NRAS codon 61 mutations. One third of CMM (10/30) had various BRAF mutations of codon 600, and a further 6% (2/31) showed NRAS codon 61 mutations. Seventeen SN tested for loss of heterozygosity (LOH) at 9p and 10q regions, known to be frequently deleted in melanoma, showed LOH at the 9p loci D9S942 and IFNA. A further lesion was found with low-level microsatellite instability at one locus, D10S214. The low rate of RAS-RAF mutations (2/22, 9.1%) observed in SN suggests that these lesions harbor as yet undetected activating mutations in other components of the RAS-RAF-MEK-ERK-MAPK pathway. Germline DNA from members of 111 multiple-case melanoma families, representing a range of known (CDKN2A) and unknown predisposing gene defects, was analyzed for germline BRAF mutations, but none was found.  相似文献   

14.
Background  Distinguishing banal melanocytic aggregates contiguous with malignant melanoma can be a histological challenge but is essential because of the potential for a spurious Breslow measurement.
Objectives  Our aim was to ascertain whether the histological distinction between the two relates to differences in the prevalence of mutations in genes significant in melanomagenesis.
Methods  Mutations in BRAF codon 600, NRAS1 codons 12/13, NRAS2 codons 60/61 and KRAS codons 12/13 were ascertained in 18 cases of primary cutaneous malignant melanoma contiguous with banal melanocytic aggregates using laser capture microdissection.
Results  Overall, 12 of 18 cases (67%) exhibited a mutation in at least one gene. BRAF  V600E appeared to be the most commonly mutated gene in both the melanocytic aggregate (seven of 18, 39%) and the melanoma (four of 18, 22%). Both populations demonstrated a similar BRAF genomic profile in 11 of 18 cases (61%) (two BRAF  V600E, nine BRAF -WT), a similar KRAS genomic profile in 14 of 18 cases (78%) (one KRAS  G12V, 13 KRAS- WT) and a similar NRAS2 genomic profile in 14 of 18 cases (all WT). Of interest, we noted a relatively high prevalence of KRAS mutations (five of 18, 28%). The frequency of KRAS mutations in the melanocytic aggregate (five of 18, 28%) was second to BRAF  V600E, while in melanoma, the frequency was also second to BRAF  V600E but equalled that of NRAS2 (1 of 18, 6%). No NRAS1 mutations were observed. BRAF and RAS mutations appeared to be mutually exclusive with only three of 18 cases (17%) demonstrating a mutation in both genes (melanocytic aggregate only).
Conclusions  Our findings hint towards the interpretation of banal melanocytic aggregates serving as precursor lesions.  相似文献   

15.
Mutations in the ras genes are key events in the process of carcinogenesis; in particular, point mutations in codon 61 of exon 2 of the N-ras gene occur frequently in cutaneous melanoma. To investigate whether these mutations occur in early or late tumor progression phases, we searched for point mutations in the N- and K-ras genes in 69 primary cutaneous melanoma, 35 metastases, and seven nevocellular nevi in association with cutaneous melanoma. Lesions were microdissected in order to procure pure tumor samples from the distinctive growth phases of the cutaneous melanoma; the very sensitive denaturing gradient gel electrophoresis technique was used to visualize the mutations, and was followed by sequencing. Point mutations in the N-ras gene but not in the K-ras gene were detected on denaturing gradient gel electrophoresis. Twenty-three primary (33%) and nine metastatic (26%) melanomas showed bandshifts for N-ras. In the majority of cases, mutations occurring in early growth phases (i.e., the "intraepidermal" radial growth phase), were preserved in later growth phases (i.e., the invasive radial growth phase, vertical growth phase, and metastatic phase), which proves the clonal relationship between the successive growth phases. In three cases, however, the mutations differed between the distinctive growth phases within the same cutaneous melanoma, due to the occurrence of an additional mutation (especially in codon 61) in a later tumor progression phase. Our approach also permitted us to analyze the mutational status of nevi, associated with cutaneous melanoma. Six out of seven associated nevi carried the same sequence (mutated or wild-type) as the primary cutaneous melanoma, whereas in one case the sequence for N-ras differed between the primary melanoma and the associated nevus. In conclusion, this approach allowed us to demonstrate the clonal relationship between subsequent growth phases of melanoma and associated nevi; our results suggest that N-ras exon 1 mutations preferentially occur during early stages of tumor progression and hence may be involved in melanoma initiation, whereas those in N-ras exon 2 are found preferentially during later stages and hence are more probably involved in metastatic spread of cutaneous melanoma.  相似文献   

16.
Melanocytic nevi are the most potent risk factors for melanoma yet identified. Variation in the nevus phenotype within a population is predominantly genetically determined. Genes that determine nevus expression may therefore act as low penetrance melanoma susceptibility genes. Rare germline mutations in CDKN2A predispose to melanoma and appear to be nevogenic, although the correlation between nevus phenotype and mutation status is poor. It is plausible that more common CDKN2A variants may influence both melanoma susceptibility and nevus susceptibility. Ala148Thr is a G to A missense polymorphism of CDKN2A, which is found in 4%-6% of the general population. We have investigated the role of Ala148Thr as a low penetrance melanoma or nevus susceptibility allele in two separate groups of individuals. The first was a sample of 488 adults recruited from 179 families of patients with the atypical nevus phenotype and/or a family history of melanoma, and the second was a population-based sample of 599 women. Similar prevalences of Ala148Thr (4.9% and 5.2%) were found in both samples but significant variation in the prevalence of the polymorphism was seen across geographic areas within England. There was no association between Ala148Thr status and nevus number or history of melanoma, and therefore the results did not support the hypothesis that the Ala148Thr variant is a low penetrance melanoma or nevus susceptibility allele. A significant protective role of Ala148Thr on the number of atypical nevi was observed in the family sample (mean of 1 atypical nevus in those with the allele and 3.5 nevi in those without, p = 0.02). After allowing for potential confounders this was not evident in the population-based sample.  相似文献   

17.
The distinction between primary melanoma and melanoma metastatic to the skin has major prognostic implications. We report a case of a 67-year-old male with a diagnosis of a superficial spreading melanoma (stage IB) rendered 6 years earlier who presented clinically with an atypical nevus on his left thigh. Histopathological examination showed an intraepidermal melanocytic proliferation that was interpreted as melanoma in situ. Subsequently, 45 additional pigmented macules appeared in crops over a 9-month period. Clinically and dermoscopically, these lesions were extremely polymorphic. Histopathological findings were compatible with melanoma in situ, as each lesion consisted of a wholly intraepidermal proliferation of markedly atypical melanocytes arranged singly and in nests. A complete gastrointestinal study showed multiple pigmented metastatic lesions throughout the stomach and small bowel, which supported a diagnosis of metastatic melanoma with gastrointestinal and epidermotropic skin involvement. Monosomy of chromosome 9 and a BRAF V600E mutation were detected in the primary tumor sample and in macro-dissected secondary lesions. No CDKN2A or CDK4 germline mutations were found. Intraepidermal epidermotropic metastases of melanoma have been rarely described in literature. In this case, histopathology alone was insufficient to distinguish metastatic melanoma from multiple in situ melanomas. The recognition of epidermotropic metastases should be based on the correlation between clinical, dermoscopic, histopathological and molecular findings.  相似文献   

18.
The characteristics of sebaceous gland hyperplasia (SGH) consist of yellowish or skin-colored papules and nodules. Chronic sun exposure and immunosuppressed conditions are the main environmental risk factors, whereas chronological aging regulated by hormones and molecular changes are the intrinsic risk factors. We have evaluated the contribution of BRAF, K-Ras, and N-Ras mutations to the pathogenesis of SGHs in four patients belonging to three MYH-associated polyposis (MAP) pedigrees. MAP is an autosomal-recessive disease characterized by multiple colorectal adenomas and cancer. Immunohistochemistry of mismatch repair and APC proteins was performed. DNA isolated from blood lymphocytes and formalin-fixed or paraffin-embedded SGHs was PCR amplified and sequenced. In the SGH patients, we detected T1796A heterozygous substitution (V600E) in the BRAF gene. Compound biallelic germline MYH mutations (Y165C/G382D, R168H/379delC, and Y90X/delGGA464) were detected in the MAP patients. In contrast to the majority of melanocytic lesions, activating hotspot mutations in BRAF have not been involved so far in the pathogenesis of SGH. BRAF mutation is not a specific marker of melanocytic cancerogenesis, and it can also be involved in SGHs. In both melanocytic and non-melanocytic skin tumors, BRAF mutation is linked to early tumorigenesis events.  相似文献   

19.
Abstract:  This study investigated the numbers of melanocytic nevi in Turkish children and adolescents. The research was conducted on 2783 subjects (age range, 7–14 yrs) at three elementary schools in Malatya, Turkey (latitude 38°N). Numbers of melanocytic nevi per subject were counted using a standard international protocol. Comparisons were made with subjects categorized according to age, sex and skin type. The mean melanocytic nevus count was 1.07 ± 2.37. A significant positive correlation was found between nevus count and age (p < 0.001). The mean count for boys was significantly higher than that for girls (p   < 0.001). Subjects with skin type II had a higher mean melanocytic nevus count than the other three groups. This is the first study related to numbers of melanocytic nevi in Turkey. The findings reveal that Turkish children and adolescents have few melanocytic nevi compared to those elsewhere in the world. In line with previous reports on other populations, analysis showed that older age, skin type II, and male sex are associated with higher melanocytic nevus counts. The results underline the importance of ethnic background in melanocytic nevus development.  相似文献   

20.
BACKGROUND: BRAF is a member of the RAF kinase family, and it promotes signaling through the RAS-MAP kinase signal transduction cascade. Research has shown that a majority of melanomas and nevi exhibit an activating V600E (T1799A) mutation in BRAF exon 15. Additional studies of BRAF have demonstrated that the T1799A mutation is absent in uveal melanomas and Spitz nevi. METHODS: The ligase detection reaction (LDR) is a sensitive technique that can identify specific DNA mutations occurring at very low frequency within heterogeneous clinical samples, and it has previously been used to analyze mutations in paraffin-embedded tissue specimens. RESULTS: The LDR can readily detect mutations in DNA extracted from non-microdissected paraffin-embedded sections of common nevi, dysplastic nevi, and melanomas. In addition, this method demonstrated the absence of the V600E (T1799A) mutation within Spitz nevi. CONCLUSION: The LDR is a highly sensitive and specific test for detecting mutations in formalin-fixed tissue. The LDR can be easily adapted to detect any mutation associated with a cutaneous disorder. The absence of the BRAF V600E mutation in Spitz's nevi may serve as a molecular signature to distinguish these lesions from common nevi, dysplastic nevi, and some types of malignant melanoma.  相似文献   

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