TY - JOUR
T1 - Frequencies of NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma
AU - Greene, Victoria R.
AU - Johnson, Marcella M.
AU - Grimm, Elizabeth A.
AU - Ellerhorst, Julie A.
N1 - Funding Information:
We sincerely appreciate the technical efforts of Ms Carolyn Cooke and Ms Marilyn Johnson. We are also indebted to Dr Jeffrey Gershenwald and Dr Victor Prieto for their efforts in the establishment and maintenance of the Melanoma Program Informatics, Tissue Resource, and Pathology Core. This work was supported by NIH P50 CA093459 (E.A.G., V.R.G., M.M.J., J.A.E.) and NIH CA16672 (DNA analysis facility). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
PY - 2009/6
Y1 - 2009/6
N2 - A lack of consensus exists with regards to the relative rates of NRAS and BRAF mutations in the radial (RGP) and vertical (VGP) growth phases of individual melanoma tumors. This study was conducted to test the hypothesis that mutations are acquired with progression from RGP to VGP. Using laser capture microdissection, pure tumor DNA was obtained from 15 in situ melanomas, and from the RGP and VGP of 29 invasive tumors. NRAS exon 2 and BRAF exon 15 DNA were amplified by PCR and sequenced. Mutations were present in 6 of 15 in situ melanomas (40). Of 29 invasive tumors, 16 exhibited RGP mutations (55.2); 22 showed VGP mutations (75.9). Paired RGPVGP mutation analysis revealed a trend toward discordance in the distribution of mutations, favoring VGP localization (P0.07). Of 15 samples, 12 with mutations in both phases had an increased proportion of mutated DNA in the VGP, measured on DNA chromatograms (P0.08). Limitations of this study include a relatively small sample cohort selected for technical reasons from a larger population, presenting the risk of selection bias. These concerns notwithstanding our findings support the hypothesis that NRAS and BRAF mutations increase with tumor progression from superficial to invasive disease.
AB - A lack of consensus exists with regards to the relative rates of NRAS and BRAF mutations in the radial (RGP) and vertical (VGP) growth phases of individual melanoma tumors. This study was conducted to test the hypothesis that mutations are acquired with progression from RGP to VGP. Using laser capture microdissection, pure tumor DNA was obtained from 15 in situ melanomas, and from the RGP and VGP of 29 invasive tumors. NRAS exon 2 and BRAF exon 15 DNA were amplified by PCR and sequenced. Mutations were present in 6 of 15 in situ melanomas (40). Of 29 invasive tumors, 16 exhibited RGP mutations (55.2); 22 showed VGP mutations (75.9). Paired RGPVGP mutation analysis revealed a trend toward discordance in the distribution of mutations, favoring VGP localization (P0.07). Of 15 samples, 12 with mutations in both phases had an increased proportion of mutated DNA in the VGP, measured on DNA chromatograms (P0.08). Limitations of this study include a relatively small sample cohort selected for technical reasons from a larger population, presenting the risk of selection bias. These concerns notwithstanding our findings support the hypothesis that NRAS and BRAF mutations increase with tumor progression from superficial to invasive disease.
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U2 - 10.1038/jid.2008.374
DO - 10.1038/jid.2008.374
M3 - Article
C2 - 19037234
AN - SCOPUS:67349167716
SN - 0022-202X
VL - 129
SP - 1483
EP - 1488
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -