title: CXCR4 pathway associated with family history of melanoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, 45 Francis St, 221L, Boston, MA, 02115, USA.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Li
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.forename: Hans R
authors.initials: HR
authors.lastname: Widlund
authors.forename: Mick
authors.initials: M
authors.lastname: Correll
authors.forename: Yaoyu E
authors.initials: YE
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.forename: Alvaro Laga
authors.initials: AL
authors.lastname: Canales
authors.forename: Shaowei
authors.initials: S
authors.lastname: Wu
authors.forename: Todd
authors.initials: T
authors.lastname: Golub
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hoshida
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: George
authors.initials: G
authors.lastname: Murphy
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D012333:RNA, Messenger; D019718:Receptors, CXCR4