A region of consistent deletion in neuroblastoma maps within human chromosome 1p36.2-36.3.

Abstract

Deletion of the short arm of human chromosome 1 is the most common cytogenetic abnormality observed in neuroblastoma. To characterize the region of consistent deletion, we performed loss of heterozygosity (LOH) studies on 122 neuroblastoma tumor samples with 30 distal chromosome lp polymorphisms. LOH was detected in 32 of the 122 tumors (26%). A single region of LOH, marked distally by DIZ2 and proximally by DIS228, was detected in all tumors demonstrating loss. Also, cells from a patient with a constitutional deletion of lp36, and from a neuroblastoma cell line with a small lp36 deletion, were analyzed by fluorescence in situ hybridization. Cells from both sources had interstitial deletions of lp36.2-36.3 which overlapped the consensus region of LOH defined by the tumors. Interstitial deletion in the constitutional case was confirmed by allelic loss studies using the panel of polymorphic markers. Four proposed candidate genes-DAN, ID3 (heir-i), CDC2L1 (p58), and TNFR2-were shown to lie outside of the consensus region of allelic loss, as defined by the above deletions. These results more precisely define the location of a neuroblastoma suppressor gene within lp36.2-36.3, eliminating 33 centimorgans of proximal lp36 from consideration. Furthermore, a consensus region of loss, which excludes the four leading candidate genes, was found in all tumors with lp36 LOH.

Detailed deletion mapping of chromosome band 14q32 in human neuroblastoma defines a 1.1-Mb region of common allelic loss

“…No MSI was observed in this study, in good agreement with those in previous reports (Schleiermacher et al, 1994;White et al, 1995). MSI is thus not generally involved in the tumorigenesis in NB.…”

Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature

“…The frequently observed GGP tumors are as follows: GGP1a tumors with both 1p loss and MYCN amplification and GGP3s tumors with 11q loss but without MYCN amplification. The former may belong to a typical MYCN-amplified neuroblastoma (White et al, 1995) with a 5-year cumulative survival rate of 42% in our series, whereas the latter to the so-called intermediate type tumor (Srivatsan et al, 1993;Attiyeh et al, 2005) with the rate of 75%. In GGP tumors, it is obvious that MYCN amplification has the most powerful impact on the patient prognosis.…”

Clinical Categories of Neuroblastoma Are Associated with Different Patterns of Loss of Heterozygosity on Chromosome Arm 1p

“…Chromosomal map locations of loci were taken from available references: Genemap98 for chromosome 1 (www.ncbi.nlm.nih.gov/genemap98/), White et al, 20 Maris et al, 21 Matise TC (http://linkage.rockefeller.edu/chr1/da- ta/genmap/chr1), and Marshfield Genetic map for chromosome 1 (www.marshmed.org/genetics/maps). Markers were initially selected to provide relatively even distribution throughout 1p at 10 to 20-cM intervals and including regions previously determined to be frequently lost in NB.…”