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CXCR4 pathway associated with family history of melanoma

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Abstract

Purpose

Genetic predisposition plays a major role in the etiology of melanoma, but known genetic markers only account for a limited fraction of family-history-associated melanoma cases. Expression microarrays have offered the opportunity to identify further genomic profiles correlated with family history of melanoma. We aimed to distinguish mRNA expression signatures between melanoma cases with and without a family history of melanoma.

Methods

Based on the Nurses’ Health Study, family history was defined as having one or more first-degree family members diagnosed with melanoma. Melanoma diagnosis was confirmed by reviewing pathology reports, and tumor blocks were collected by mail from across the USA. Genomic interrogation was accomplished through evaluating expression profiling of formalin-fixed paraffin-embedded tissues from 78 primary cutaneous invasive melanoma cases, on either a 6K or whole-genome (24K) Illumina gene chip. Gene set enrichment analysis was performed for each batch to determine the differentially enriched pathways and key contributing genes.

Results

The CXC chemokine receptor 4 (CXCR4) pathway was consistently up-regulated within cases of familial melanoma in both platforms. Leading edge analysis showed four genes from the CXCR4 pathway, including MAPK1, PLCG1, CRK, and PTK2, were among the core members that contributed to the enrichment of this pathway. There was no association between the enrichment of CXCR4 pathway and NRAS, BRAF mutation, or Breslow thickness of the primary melanoma cases.

Conclusions

We found that the CXCR4 pathway might constitute a novel susceptibility pathway associated with family history of melanoma in first-degree relatives.

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Acknowledgments

We are grateful to Drs. Alisa M. Goldstein and Nan Hu at Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, for their comments on our revisions. We thank the participants and staff of the Nurses’ Health Study, for their valuable contributions as well as the following state cancer registries for their help: A.L., A.Z., A.R., C.A., C.O., C.T., D.E., F.L., G.A., I.D., I.L., I.N., I.A., K.Y., L.A., M.E., M.D., M.A., M.I., N.E., N.H., N.J., N.Y., N.C., N.D., O.H., O.K., O.R., P.A., R.I., S.C., T.N., T.X., V.A., W.A., W.Y. This work was supported by Department of Dermatology, Brigham and Women’s Hospital, Boston, Massachusetts, a Nurses’ Health Study Grant (P01 CA87969). The funding sources did not involve in the data collection, data analysis, manuscript writing, and review.

Conflict of interest

AAQ serves as a consultant for Abbott, Centocor, Novaritis, and the Centers for Disease Control and Prevention. The other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, 45 Francis St, 221L, Boston, MA, 02115, USA

    Wen-Qing Li, Jiali Han, Hans R. Widlund, Shaowei Wu, Thomas S. Kupper & Abrar A. Qureshi

  2. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Jiali Han, David J. Hunter & Abrar A. Qureshi

  3. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Jiali Han & David J. Hunter

  4. Center for Cancer Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    Mick Correll, Yaoyu E. Wang & John Quackenbush

  5. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    Martin C. Mihm

  6. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    Alvaro Laga Canales & George Murphy

  7. Broad Institute, Harvard Medical School, Boston, MA, USA

    Todd Golub & Yujin Hoshida

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  1. Wen-Qing Li
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Correspondence to Abrar A. Qureshi.

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Li, WQ., Han, J., Widlund, H.R. et al. CXCR4 pathway associated with family history of melanoma. Cancer Causes Control 25, 125–132 (2014). https://doi.org/10.1007/s10552-013-0315-9

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  • DOI: https://doi.org/10.1007/s10552-013-0315-9

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