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| LOSS OF HETEROZYGOSITY FOR CHROMOSOME-1 OR CHROMOSOME-14 DEFINES SUBSETS OF ADVANCED NEUROBLASTOMAS |
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| Author(s): FONG CT, WHITE PS, PETERSON K, SAPIENZA C, CAVENEE WK, KERN SE, VOGELSTEIN B, CANTOR AB, LOOK AT, BRODEUR GM |
| Source: CANCER RESEARCH Volume: 52 Issue: 7 Pages: 1780-1785 Published: APR 1 1992 |
| Times Cited: 168 References: 32 |
| Abstract: Neuroblastomas have been characterized genetically by N-myc amplification and by deletions or loss of heterozygosity (LOH) for the short arm of chromosome 1. However, recent studies have suggested deletion or allelic loss involving at least three other chromosome arms, 11q, 14q, and 17p. Therefore, we undertook an analysis of allelic loss for these respective chromosomal arms to determine the frequency and pattern of LOH as well as the correlation of these findings with other biological and clinical variables. A group of 24 pairs of normal and tumor DNAs was chosen that were representative of patients of different ages and stages. A substantial frequency of LOH (greater-than-or-equal-to 20%) was found only for 1p and 14q, whereas LOH for the other chromosome arms occurred in less-than-or-equal-to 5% of cases. On the basis of these results, we extended the analysis to a total of 59 neuroblastomas, and we found 1p LOH in 15 of the 59 cases (25%) and 14q LOH in 10 of 43 informative cases (23%). N-myc amplification was found in 15 of the 59 cases (25%). This analysis confirmed that 1p LOH and 14q LOH occurred almost exclusively in patients with advanced stages of disease. Furthermore, LOH for 1p and 14q usually occurred independent of each other, and 1p LOH frequently was associated with N-myc amplification, whereas 14q LOH was not. Thus, our results demonstrate that neuroblastomas are complex genetically and that there are at least two distinct loci for putative suppressor genes that are deleted independently in this tumor, both of which are associated with advanced stages of disease. |
| Document Type: Article |
| Language: English |
Addresses:
1. WASHINGTON UNIV, SCH MED, DEPT PEDIAT, 400 S KINGSHIGHWAY BLVD, ST LOUIS, MO 63110 USA
2. PEDIAT ONCOL GRP, ST LOUIS, MO 63110 USA
3. LUDWIG INST CANC RES, MONTREAL H3A 1A1, QUEBEC CANADA
4. JOHNS HOPKINS UNIV, DEPT ONCOL, BALTIMORE, MD 21205 USA
5. JOHNS HOPKINS UNIV, DEPT PATHOL, BALTIMORE, MD 21205 USA
6. ST JUDE CHILDRENS HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38101 USA
7. PEDIAT ONCOL GRP, OFF STAT, GAINESVILLE, FL 32608 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: HL505 |
| ISSN: 0008-5472 |
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