Weak linkage at 4p16 to predisposition for human neuroblastoma.

Abstract:

:The most frequent genetic alterations described in neuroblastoma (NB) are amplification of MYCN oncogene and deletion of chromosome 1p, although somatic deletions have been demonstrated at other chromosomal intervals. Since loss of heterozygosity (LOH) at distal 4p has been observed in about 20-29% of neuroblastomas, we have evaluated deletions in 41 Italian NB samples by LOH analysis at loci mapping to 4p as follows: pter-D4S2936-D4S412-D4S2957-D4S432-D4S3023-D4S431-cen. Our analysis showed allele losses in eight out of 41 samples (19.5%) and allowed the identification of a smallest region of overlapping deletion (SRO) of 3.0 cM, delimited by D4S412 and D4S3023. Two of these tumors with 4p LOH are from patients belonging to a family with recurrent NB. Interestingly the genotyping of this family revealed an identical haplotype that includes the nonrecombinant loci D4S412, D4S2957 and D4S432 shared by all affected children and demonstrated that this haplotype is retained in the two tumors carrying somatic deletions from patients of this family. Furthermore linkage analysis was performed in two NB families and yielded an overall lod-score of 3.0 in the interval including the haplotype. This provides a confirmatory indication that the region delimited by D4S2936 and D4S3023, which also includes the new defined SRO, may harbor NB predisposing gene/s.

journal_name

Oncogene

journal_title

Oncogene

authors

Perri P,Longo L,Cusano R,McConville CM,Rees SA,Devoto M,Conte M,Ferrara GB,Seri M,Romeo G,Tonini GP

doi

10.1038/sj.onc.1206009

subject

Has Abstract

pub_date

2002-11-28 00:00:00

pages

8356-60

issue

54

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

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