Mitf-Mdel, a novel melanocyte/melanoma-specific isoform of microphthalmia-associated transcription factor-M, as a candidate biomarker for melanoma
Melanoma incidence is on the rise, and advanced melanoma carries an extremely poor prognosis. Treatment options, including chemotherapy and immunotherapy, are limited and offer low response rates and transient efficacy.
Thus, identification of new melanocyte/melanoma antigens that serve as potential novel candidate biomarkers in melanoma is an important area for investigation.
Methods: Full length MITF-M and its splice variant cDNA were cloned from human melanoma cell line 624mel by RT-PCR. Expression was investigated using regular and quantitative RT-PCR in 3 normal melanocytes (NHEM), 31 melanoma cell lines, 21 frozen melanoma tissue samples, 18 blood samples (PBMC) from healthy donors, and 12 non-melanoma cancer cell lines, including 3 breast, 5 glioma, 1 sarcoma, 2 kidney, and 1 ovarian cancer cell lines.
Results: A novel splice variant of MITF-M, which we named MITF-Mdel, was identified.
The predicted MITF-Mdel protein contains two in frame deletions, 56- and 6- amino acid deletions in exon 2 (from V32 to E87) and exon 6 (from A187 to T192), respectively. MITF-Mdel was widely expressed in melanocytes, melanoma cell lines and tissues, but almost undetectable in non-melanoma cell lines or PBMC from healthy donors.
Both isoforms were expressed significantly higher in melanoma tissues than in cell lines. Two of 31 melanoma cell lines expressed only one isoform or the other.
Conclusion: MITF-Mdel, a novel melanocyte/melanoma-specific isoform of MITF-M, may serve as a potential candidate biomarker for diagnostic and follow-up purposes in melanoma.
Author: Yixiang WangSoroosh RadfarSuhu LiuAdam RikerHung Khong
Credits/Source: BMC Medicine 2010, 8:14
Published on: 2010-02-17
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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