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INVITED SPEAKERS ABSTRACTS

Genetic determinants of disease progression and survival in melanoma

Newton-Bishop, J.

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doi: 10.1097/01.cmr.0000382760.70624.24
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Staging of melanoma and prognostic estimations are currently based upon a number of histological characteristics (such as thickness, mitotic rate and the presence of ulceration [1]), which are markers of key genetic changes in the tumour. In recent years considerable progress has been made in understanding these changes, so that the identification of mutations in BRAF and NRAS, leading to constitutive mitogen-activated protein kinase (MAPK) pathway as well as constitutive activity in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, were recognized as critical events in melanoma progression [2], and have already lead to the development of novel therapeutic strategies. Furthermore there is more known about biological differences between melanomas in different body sites, which are consequent upon different genetic events in those tumours [3].

The development of genomic platforms which allow system-wide investigation of genetic changes in tumours and platforms specifically developed for use in paraffin embedded tumours, have lead to progress in identifying prognostic markers [4,5]. We remain some way away however from the development of validated markers for use in clinical practice.

Just as susceptibility to melanoma is determined by hereditary genetic variation and environmental exposures, however, it is likely that survival is determined by hereditary variation in genes having an effect on tumour/host interaction and environmental exposures and the research community is moving towards understanding these complex interactions.

References

1. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27:6199–6206.
2. Smalley KS. Understanding melanoma signaling networks as the basis for molecular targeted therapy. J Invest Dermatol 130:28–37.
3. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005; 353:2135–2147.
4. Conway C, Mitra A, Jewell R, Randerson-Moor J, Lobo S, Nsengimana J, et al. Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival. Clin Cancer Res 2009; 15:6939–6946.
5. Winnepenninckx V, Lazar V, Michiels S, Dessen P, Stas M, Alonso SR, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst 2006; 98:472–482.
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