title: Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma.
abstract: OBJECTIVE
  The development of a genetic signature for the identification of high-risk cutaneous melanoma tumors would provide a valuable prognostic tool with value for stage I and II patients who represent a remarkably heterogeneous group with a 3% to 55% chance of disease progression and death 5 years from diagnosis.
  
  
  METHODS
  A prognostic 28-gene signature was identified by analysis of microarray expression data. Primary cutaneous melanoma tumor tissue was evaluated by RT-PCR for expression of the signature, and radial basis machine (RBM) modeling was performed to predict risk of metastasis.
  
  
  RESULTS
  RBM analysis of cutaneous melanoma tumor gene expression reports low risk (class 1) or high risk (class 2) of metastasis. Metastatic risk was predicted with high accuracy in development (ROC = 0.93) and validation (ROC = 0.91) cohorts of primary cutaneous melanoma tumor tissue. Kaplan-Meier analysis indicated that the 5-year disease-free survival (DFS) rates in the development set were 100% and 38% for predicted classes 1 and 2 cases, respectively (P < 0.0001). DFS rates for the validation set were 97% and 31% for predicted classes 1 and 2 cases, respectively (P < 0.0001). Gene expression profile (GEP), American Joint Committee on Cancer stage, Breslow thickness, ulceration, and age were independent predictors of metastatic risk according to Cox regression analysis.
  
  
  CONCLUSIONS
  The GEP signature accurately predicts metastasis risk in a multicenter cohort of primary cutaneous melanoma tumors. Preliminary Cox regression analysis indicates that the signature is an independent predictor of metastasis risk in the cohort presented.
authors.affiliation: Northwestern University School of Medicine, Chicago, Illinois. pgerami@nmff.org.
authors.forename: Pedram
authors.initials: P
authors.lastname: Gerami
authors.affiliation: Castle Biosciences, Inc., Friendswood, Texas.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Cook
authors.affiliation: St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors.forename: Jeff
authors.initials: J
authors.lastname: Wilkinson
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Russell
authors.affiliation: Cancer Treatment Centers of America, Newnan, Georgia.
authors.forename: Navneet
authors.initials: N
authors.lastname: Dhillon
authors.affiliation: University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Rodabe N
authors.initials: RN
authors.lastname: Amaria
authors.affiliation: University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lyle
authors.affiliation: Castle Biosciences, Inc., Friendswood, Texas.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Johnson
authors.affiliation: Castle Biosciences, Inc., Friendswood, Texas.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Oelschlager
authors.affiliation: The Kelsey Seybold Clinic, Houston, Texas.
authors.forename: Gilchrist L
authors.initials: GL
authors.lastname: Jackson
authors.affiliation: Kelsey Research Foundation, Houston, Texas.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Greisinger
authors.affiliation: Castle Biosciences, Inc., Friendswood, Texas.
authors.forename: Derek
authors.initials: D
authors.lastname: Maetzold
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Delman
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia.
authors.forename: David H
authors.initials: DH
authors.lastname: Lawson
authors.affiliation: St. Joseph's Hospital and Medical Center, Phoenix, Arizona.
authors.forename: John F
authors.initials: JF
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D012307:Risk Factors; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins