Paul A. Voute

Chromosome bands 1p35-36 contain two distinct neuroblastoma tumor suppressor loci, one of which is imprinted.

A previous loss of heterozygosity (LOH) study of a series of 91 neuroblastomas suggested that the 1p35–36 region encodes at least two tumor suppressor genes (TSGs) of importance in neuroblastoma development. Here we present the results of a study including 205 neuroblastomas that were analyzed for LOH at chromosome 1 and MYCN amplification. The results corroborate the existence of two TSGs on 1p. Distinct 1p loci seem to be involved in MYCN single copy vs. MYCN amplified neuroblastoma, as these tumors display a different type of shortest region of overlap (SRO). About 15% of MYCN single copy neuroblastomas show 1p deletions of variable length with an SRO of 47 cR at 1p36.3. The lost alleles are preferentially of maternal origin (P = 0.0002), suggesting parental imprinting of the locus. MYCN amplified neuroblastomas have a contrasting pattern of 1p loss. These tumors display much larger deletions of at least 89 cR comprising the region from 1p36.1 to the telomere. LOH of 1p is detected in 86% of the cases. The lost alleles are of random parental origin, suggesting inactivation of a non‐imprinted TSG.

A Cytogenetic study of Wilms' Tumor

Cytogenetic studies were attempted on a sample of 33 Wilms tumors using short- and long-term tissue culture techniques; most were studied after 2-13 wk in vitro. Abnormal karyotypes were found in 11 tumors, 10 of which had been treated previously with radiotherapy and/or chemotherapy. Insufficient growth of 17 tumors prevented cytogenetic analysis, and in 5 only normal karyotypes were found. Of the 11 tumors with abnormalities, 9 had modes within the diploid range, 1 was hypertriploid, and 1 showed hypodiploid variation. Except for chromosome #5, all chromosomes were involved in structural and numeric changes. Three tumors showed variation in the short arm of chromosome #11, and abnormalities of chromosomes #1, #3, #7, #9, #10, and #14 occurred in more than one tumor. A predisposition to Wilms tumor is associated with a constitutional deletion of 11p13. From the present study, it is apparent that a similar cytogenetic change may play a primary role in the development of Wilms tumor in normal individuals.

Amore protocol in pediatric head and neck rhabdomyosarcoma: Descriptive analysis of failure patterns

The AMORE protocol is a local treatment for patients with nonorbital pediatric head and neck rhabdomyosarcoma (HNRMS). The objectives of this study were: (1) to assess the adequacy of the concept, and (2) to identify factors associated with relapse.

Reconstructive surgery as part of the AMORE protocol in the treatment of pediatric head and neck soft tissue sarcoma

Abstractu2002For advanced stage residual or recurrent paediatric soft tissue sarcomas in the head and neck area, the AMORE protocol was developed in our hospital. It consists of Ablative surgery, afterloading brachytherapy, using a MOulage technique and REconstructive surgery in 1 week. The reconstructive surgical component of this treatment regimen was reviewed. Between January 1993 and November 1999, 18 children with soft tissue sarcomas in the head and neck area were treated according to the AMORE protocol. The median follow-up was 31.5 months (range 2 months to 6.5 years). For reconstruction, a free vascularized muscle transfer was performed in 12 patients and a pedicled muscle transposition in six patients. The surgical reconstruction was successful in all but one patient and in 16 of 18 patients, healing was uneventful. Since the introduction of this multidisciplinary approach in the treatment of paediatric soft tissue sarcomas in the head and neck region, the results have been promising. The immediate reconstruction of an irradiated, contaminated wound bed with uncompromised, well-vascularized muscle tissue has, in general, resulted in excellent wound healing. The treatment was undertaken in a limited amount of time and resulted in an acceptable morbidity.