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A purpose-built high-resolution array with 93.75% breakpoint accuracy was used to map 4000 patients with diverse diagnoses and identify eight probands harboring microdeletions at TP53 (17p13.1), a DNA copy-number variations (CNVs) which might cause childhood-onset developmental delay (DD) and cancer. The results revealed a possible association of 17p13.1 CNVs with distinct phenotypes depending on the position of the breakpoint with respect to TP53 and called for further studies to determine if other loci in the genome also give rise to phentotypically distinct disorder.

Pediatric de novo acute myeloid leukemia (AML) is an aggressive malignancy with current therapy resulting in cure rates of only 60%. To better understand the cause of the marked heterogeneity in therapeutic response and to identify new prognostic markers and therapeutic targets a comprehensive list of the genetic mutations that underlie the pathogenesis of AML is needed. To approach this goal, we examined diagnostic leukemic samples from a cohort of 111 children with de novo AML using single-nucleotide-polymorphism microarrays and candidate gene resequencing. Our data demonstrate that, in contrast to pediatric acute lymphoblastic leukemia (ALL), de novo AML is characterized by a very low burden of genomic alterations, with a mean of only 2.38 somatic copy-number alterations per leukemia, and less than 1 nonsynonymous point mutation per leukemia in the 25 genes analyzed. Even more surprising was the observation that 34% of the leukemias lacked any identifiable copy-number alterations, and 28% of the leukemias with recurrent translocations lacked any identifiable sequence or numerical abnormalities. The only exception to the presence of few mutations was acute megakaryocytic leukemias, with the majority of these leukemias being characterized by a high number of copy-number alterations but rare point mutations. Despite the low overall number of lesions across the patient cohort, novel recurring regions of genetic alteration were identified that harbor known, and potential new cancer genes. These data reflect a remarkably low burden of genomic alterations within pediatric de novo AM L, which is in stark contrast to most other human malignancies. copy number alterations | single-nucleotide-polymorphism (SNP) | microarray | candidate gene resequencing | loss-of-heterozygosity (LOH)

A study was conducted to assess the genetic pattern or body morphology that could be a cause to develop cancer among children. Results showed a higher prevalence among children with morphological abnormalities for developing cancer.

Byline: Mana M. Parast (1), Grant Eudy (1), Kenneth W. Gow (2), Mahul Amin (1), Bahig Shehata (3) Keywords: carcinoma; chromosome; kidney; pediatric; translocation; von Hippel-Lindau Abstract: Renal cell carcinomas (RCCs) are rare in the pediatric population when they occur, a significant percentage are associated with specific cytogenetic abnormalities and germline mutations. These include mutations in the von Hippel-Lindau (VHL) gene and translocations involving the TFE3 transcription factor gene on Xp11.2. Here we report a case of a 3-year-old child with a large renal mass. Histologic examination of the tumor showed a predominantly nested growth pattern with some papillary foci. Cytogenetic analysis revealed a karyotype of t(X 1)(p11.2 p34.3), consistent with a TFE3-associated RCC. Interestingly, sequencing of the patient's VHL gene revealed a single point mutation, previously seen in a subgroup of patients with von Hippel-Lindau disease. This is the first reported case, to our knowledge, of t(X 1)-associated RCC in a patient with concurrent VHL gene mutation. Author Affiliation: (1) Department of Pathology, Room G167, Emory University Hospital, 1364 Clifton Road NE, Atlanta, GA 30322, USA (2) Division of Pediatric Surgery, Emory University, 2040 Ridgewood Drive NE, Atlanta, GA 30322, USA (3) Department of Pathology, Children's Healthcare of Atlanta at Egleston, 1405 Clifton Road NE, Atlanta, GA 30322, USA Article History: Registration Date: 01/01/2004 Received Date: 30/01/2004 Accepted Date: 08/02/2004 Online Date: 15/07/2004

A mouse model has been generated for medulloblastoma, one of the most common types of malignancies in children. Cre-LoxP-mediated inactivation of Rb and p53 tumor suppressor genes was carried out in the external granular layer (EGL) cells of the cerebellum. Loss of function of RB seems to be essential for medulloblastoma development in the mouse. It is hypothesized that medulloblastomas come from multipotent precursor cells in the EGL.

Results of a large interview study show no significant increase in genetic disease among offspring of cancer survivors. For 2198 offspring of survivors, 3.4% had genetic disease, compared with 3.1% among 4544 offspring of controls. Cytogenetic syndromes, single-gene defects, and simple malformations also were not significantly different. The study involved adult survivors of childhood cancer who had been treated before 1976. The study had 80% power to identify an increase as low as 40%, and no such effect was found.

More than 7000 new cases of cancer are diagnosed in children under 15 years of age each year in the United States; approximately one-third of these children ultimately die from [...]

A parent who has a child with cancer appears to have no greater risk of cancer than other adults in the general population. Researchers studied cancer registry data of 11,380 parents of children with cancer in Denmark from 1943 to 1985. A total of 1,445 cancers were diagnosed in the parents, however, 1,496 cancers would be expected from national incidence rates. Childhood soft-tissue sarcomas and bone cancers, which in other studies have been associated with an increased risk for parents, were not linked to a greater risk in this study. Among 1,135 parents of children with these kind of cancers, 177 cancers were reported, compared to an expected 188.3 cancers. There was a notable excess of breast cancer cases among mothers under the age of 45 who had children with cancer diagnosed under the age of 3. The 10 extra cases represent 22% of the 45 breast cancer cases diagnosed in mothers under the age of 45.

Germline mutations in the p53 tumor-suppressor gene may occur in children and young adults with a second malignant tumor who do not have a family history of Li-Fraumeni syndrome. Mutations in the p53 gene have been identified in families with Li-Fraumeni syndrome, an inherited cancer pattern. Analysis of DNA from 59 children and young adults with a second malignant tumor found four germline mutations in the p53 gene. All of the mutations caused a change in the amino acid sequence of the cell growth protein for which the p53 gene encodes. Three of the mutations were identical to those found previously, but the fourth was a new type of mutation. Analysis of DNA from close relatives of three patients found that five had mutations in the p53 gene. Three of these relatives also had developed cancer. Sixteen other close relatives that may have a mutation in the p53 were also identified, but their DNA was not analyzed.

Wilms tumor is an embryonal kidney tumor involving complex pathology and genetics. The Wilms tumor locus on chromosome 11p13 is defined by the region of overlap of constitutional and tumor-associated [...]

The Wilms tumor locus on chromosome 11p13 has been to mapped to a region defined by overlapping, tumor-specific deletions. Complementary DNA clones representing transcripts of 2.5 (WIT-1) and 3.5 kb [...]

Neuroblastoma is the most common extracranial solid tumor of childhood, accounting for 8 to 10 percent of pediatric cancers, due to which large-scale screening programs were implemented to diagnose the disease in prognostically favorable setting of very young age and localized stage. Findings showed that many neuroblastomas in unscreened populations probably escape detection due to spontaneous regression or differentiation and low-risk cases of disease rarely evolve into stage 4 diseases.

Methods used in a Danish study that found that parents of children with cancer generally do not have a greater risk of cancer than other adults may have underestimated the risk among family members. One possibility not addressed in the study is that incidence rates could be lower among people who have children compared to people without children. Also, not all people with cancer have the relevant mutated genes and fewer of the relatives carry the genes. The study's use of the conventional diagnostic classification of cancer may not be the best approach to look for inherited susceptibility to cancer. Grouping different types of cancer according to suspected genetic or environmental causes may be a better method. However, the study is valuable and will help alleviate worries among family members of children with cancer.

The use of molecular approaches has become a part of the standard of care in the management of pediatric cancer patients. A model is presented for understanding cancer biology, using specific examples taken from pediatric oncology, and the application of molecular techniques to the clinical management of pediatric cancer patients.

Children of cancer survivors do not appear to have increased risk of congenital anomalies, according to results of a study by J. Byrne et al. The study is notable because of the large size of the study cohort. The researchers also classified the observed congenital anomalies according to whether germ-cell mutation was a likely cause. The study involved 2,198 children with a parent who had been treated for a brain tumor or malignancy during childhood or adolescence.

Apart from known genetic cancer syndromes genetic factors seem relatively unimportant in childhood cancers. A study in the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) including data on 42277 [...]