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Previous Volume 353:2243-2253 November 24, 2005 Number 21 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Perspective by Kushner, B. H. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Neuroblastoma is a childhood cancer with considerable morbidity and mortality. Tumor-derived biomarkers may improve risk stratification.

Methods We screened 915 samples of neuroblastoma for loss of heterozygosity (LOH) at chromosome bands 1p36 and 11q23. Additional analyses identified a subgroup of cases of 11q23 LOH with unbalanced 11q LOH (unb11q LOH; defined as loss of 11q with retention of 11p). The associations of LOH with relapse and survival were determined.

Results LOH at 1p36 was identified in 209 of 898 tumors (23 percent) and LOH at 11q23 in 307 of 913 (34 percent). Unb11q LOH was found in 151 of 307 tumors with 11q23 LOH (17 percent of the total cohort). There was a strong association of 1p36 LOH, 11q23 LOH, and unb11q LOH with most high-risk disease features (P<0.001). LOH at 1p36 was associated with amplification of the MYCN oncogene (P<0.001), but 11q23 LOH and unb11q LOH were not (P<0.001 and P=0.002, respectively). Cases with unb11q LOH were associated with three-year event-free and overall survival rates (±SE) of 50±5 percent and 66±5 percent, respectively, as compared with 74±2 percent and 83±2 percent among cases without unb11q LOH (P<0.001 for both comparisons). In a multivariate model, unb11q LOH was independently associated with decreased event-free survival (P=0.009) in the entire cohort, and both 1p36 LOH and unb11q LOH were independently associated with decreased progression-free survival in the subgroup of patients with features of low-risk and intermediate-risk disease (P=0.002 and P=0.02, respectively).

Conclusions Unb11q LOH and 1p36 LOH are independently associated with a worse outcome in patients with neuroblastoma.

Source Information

From Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, and Abramson Family Cancer Research Institute, Philadelphia (E.F.A., Y.P.M., Q.W., C.W., D.K., G.M.B., J.M.M.); the Children's Oncology Group, Arcadia, Calif. (E.F.A., W.B.L., Y.P.M., Q.W., D.K., P.W.M., R.C.S., A.T.L., H.S., G.M.B., S.L.C., K.K.M., J.M.M.); the Department of Statistics, University of Florida, and Children's Oncology Group, Gainesville (W.B.L., P.W.M.); Children's Hospital of Los Angeles, Los Angeles (R.C.S., H.S.); Dana–Farber Cancer Institute, Harvard Medical School, Boston (A.T.L.); the Feinberg School of Medicine, Northwestern University, Chicago (S.L.C.); and the University of California, San Francisco, School of Medicine, San Francisco (K.K.M.).

Address reprint requests to Dr. Maris at the Division of Oncology, Children's Hospital of Philadelphia, Abramson Pediatric Research Center 902A, 3615 Civic Center Blvd., Philadelphia, PA 19104-4318, or at maris{at}email.chop.edu.

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