Molecular characterisation defines clinically-actionable heterogeneity within Group 4 medulloblastoma and improves disease risk-stratification.

Group 4 tumours (MB) represent the majority of non-WNT/non-SHH medulloblastomas. Their clinical course is poorly predicted by current risk-factors. MB molecular substructures have been identified (e.

Effects of the growth pattern of medulloblastoma on short-term neurological impairments after surgery: results from the prospective multicenter HIT-SIOP PNET 4 study.

Objective: Extensive resection of a tumor in the posterior fossa in children is associated with the risk of neurological deficits. The objective of this study was to prospectively evaluate the short-term neurological morbidity in children after medulloblastoma surgery and relate this to the tumor's growth pattern and to the extent of resection.

Methods: In 160 patients taking part in the HIT-SIOP PNET 4 (Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma) trial, neurosurgeons prospectively responded to questions concerning the growth pattern of the tumor they had resected.

Variants in vincristine pharmacodynamic genes involved in neurotoxicity at induction phase in the therapy of pediatric acute lymphoblastic leukemia.

Vincristine is an important drug of acute lymphoblastic leukemia (ALL) treatment protocols that can cause neurotoxicity. Patients treated with LAL/SHOP protocols often suffer from vincristine-related neurotoxicity in early phases of treatment. A genetic variant in CEP72, a gene involved in vincristine pharmacodynamics, was recently associated with neurotoxicity after prolonged vincristine treatment.

Involvement of miRNA polymorphism in mucositis development in childhood acute lymphoblastic leukemia treatment.

Aim: Mucositis, linked to methotrexate, daunorubicin or cyclophosphamide, is a frequent childhood acute lymphoblastic leukemia (ALL) therapy side effect. miRNAs regulate the expression of pharmacokinetic/pharmacodynamic pathway genes. SNPs in miRNAs could affect their levels or function, and affect their pharmacokinetic/pharmacodynamic pathway target genes.

Involvement of SNPs in miR-3117 and miR-3689d2 in childhood acute lymphoblastic leukemia risk.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Numerous studies have shown that microRNAs (miRNAs) could play a role in this disease. Nowadays, more than 2500 miRNAs have been described, that regulate more than 50% of genes, including those involved in B-cell maturation, differentiation and proliferation.

Pharmacoepigenetics in childhood acute lymphoblastic leukemia: involvement of miRNA polymorphisms in hepatotoxicity.

Aim: Hepatotoxicity is one of the most common drug-related toxicities during the treatment of childhood acute lymphoblastic leukemia (ALL). Many genes involved in liver-specific signaling pathways are tightly controlled by miRNAs, and miRNA function could be modulated by SNPs. As a consequence, we hypothesized that variants in miRNAs could be associated with drug-induced hepatotoxicity.

Mir-pharmacogenetics of Vincristine and peripheral neurotoxicity in childhood B-cell acute lymphoblastic leukemia.

Vincristine (VCR), an important component of childhood acute lymphoblastic leukemia (ALL) therapy, can cause sensory and motor neurotoxicity. This neurotoxicity could lead to dose reduction or treatment discontinuation, which could in turn reduce survival. In this line, several studies associated peripheral neurotoxicity and polymorphisms in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) of VCR.

Confirmation of involvement of new variants at CDKN2A/B in pediatric acute lymphoblastic leukemia susceptibility in the Spanish population.

The locus CDKN2A/B (9p21.3), which comprises the tumor suppressors genes CDKN2A and CDKN2B and the long noncoding RNA (lncRNA) known as ANRIL (or CDKN2B-AS), was associated with childhood acute lymphoblastic leukemia (ALL) susceptibility in several genome wide association studies (GWAS). However, the variants associated in the diverse studies were different.

MiR-pharmacogenetics of methotrexate in childhood B-cell acute lymphoblastic leukemia.

Objectives: Methotrexate (MTX), the key drug in childhood B-cell acute lymphoblastic leukemia (B-ALL) therapy, often causes toxicity. An association between genetic variants in MTX transport genes and toxicity has been found. It is known that these transporters are regulated by microRNAs (miRNAs), and miRNA single nucleotide polymorphisms (SNPs) interfere with miRNA levels or function.

Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study.

The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001-2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse.

Vincristine pharmacokinetics pathway and neurotoxicity during early phases of treatment in pediatric acute lymphoblastic leukemia.

Aim: Vincristine is an important component of acute lymphoblastic leukemia (ALL) treatment protocols that can cause neurotoxicity. Patients treated with LAL/SHOP protocols often suffer from vincristine-related neurotoxicity in early phases of treatment. Recently, a genome-wide association study connected a SNP in CEP72, involved in vincristine pharmacodynamics, with neurotoxicity during later phases of therapy, which was not replicated during induction phase.

Disseminated fusariosis and hematologic malignancies, a still devastating association. Report of three new cases.

Background: Fungi of the genus Fusarium are primarily plant pathogens and saprobes that produce disseminated infections in immunologically deficient humans. After aspergillosis, disseminated fusariosis is the second most common cause of invasive infection by filamentous fungi in patients with hematologic malignancies or those undergoing transplants of hematopoietic progenitors.

Aims: Disseminated fusariosis (DF) is considered an extremely rare infection and has reached a stable incidence rate, but its high mortality rate and the lack of an optimal management protocol have raised increasing interest in this mycosis.

Errors in the interpretation of copy number variations due to the use of public databases as a reference.

The identification of new cryptic deletions and duplications can be used to improve prognostic classification in cancer. To obtain accurate results, it is necessary to discriminate between somatic alterations in the tumor cell and germline polymorphisms. For this purpose, copy number variation (CNV) public databases have been used as a reference.

Noncoding RNA-related polymorphisms in pediatric acute lymphoblastic leukemia susceptibility.

Background: Evidence for an inherited genetic risk for pediatric acute lymphoblastic leukemia has been provided in several studies. Most of them focused on coding regions. However, those regions represent only 1.

Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in pediatric acute lymphoblastic leukemia.

Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity.

Intron 3 of the ARID5B gene: a hot spot for acute lymphoblastic leukemia susceptibility.

Purpose: Single-nucleotide polymorphisms (SNPs) in AT-rich interactive domain 5B (ARID5B) have been associated with risk for pediatric acute lymphoblastic leukemia (ALL). After reviewing previous studies, we realized that the most significant associations were restricted to intron 3, but the mechanism(s) by which those SNPs affect ALL risk remain to be elucidated. Therefore, the aim of this study was to analyze the association between genetic variants of the intron 3 region of ARID5B and the incidence of B-ALL in a Spanish population.

Polymorphisms in the methotrexate transport pathway: a new tool for MTX plasma level prediction in pediatric acute lymphoblastic leukemia.

Objectives: Methotrexate (MTX) is an important component of therapy for pediatric acute lymphoblastic leukemia (ALL). Treatment with MTX often causes toxicity, which can necessitate dose reduction or treatment cessation. Interindividual differences in adverse reactions can be due to different factors, including polymorphisms in key genes.

Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trial.

Purpose: To compare event-free survival (EFS), overall survival (OS), pattern of relapse, and hearing loss in children with standard-risk medulloblastoma treated by postoperative hyperfractionated or conventionally fractionated radiotherapy followed by maintenance chemotherapy.

Patients And Methods: In all, 340 children age 4 to 21 years from 122 European centers were postoperatively staged and randomly assigned to treatment with hyperfractionated radiotherapy (HFRT) or standard (conventional) fractionated radiotherapy (STRT) followed by a common chemotherapy regimen consisting of eight cycles of cisplatin, lomustine, and vincristine.

Results: After a median follow-up of 4.

A prospective biological study in relation to a family with Li-Fraumeni syndrome.

Introduction: The Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disorder associated with different tumor types in childhood and young adults. Approximately 70% of LFS cases contain germline mutations in the TP53 gene. We report a case of a family suspected of LFS.

[T-cell pediatric acute lymphoblastic leukemia: analysis of survival and prognostic factors in 4 consecutive protocols of the Spanish cooperative study group SHOP].

Background And Objectives: Acute lymphoblastic leukemia (ALL) is the most frequent cancer in childhood, with cure rates of 80-85%. In T-cell ALL (15% of ALL), prognostic factors are ill defined. We aimed to describe the event-free survival (EFS) and analyze clinical prognostic factors in a series of pediatric T-ALL of 4 consecutive clinical trials.

Polymorphisms of the SLCO1B1 gene predict methotrexate-related toxicity in childhood acute lymphoblastic leukemia.

Background: Methotrexate (MTX) is an important component of the therapy for childhood acute lymphoblastic leukemia. Treatment with high-dose MTX often causes toxicity, recommending a dose reduction and/or cessation of treatment. Polymorphisms in genes involved in the MTX metabolism have been associated with toxicity with controversial results.

[Results of the SHOP LNHB98 (LMB89) trial in pediatric patients with B-cell non-Hodgkin's lymphoma].

Background And Objective: After the good results obtained by the Société Française d'Oncologie Pédiatrique (SFOP) regarding the pediatric B-type non-Hodgkin's (Burkitt and large B-cell) lymphoma and L3 leukemia, the Sociedad Española de Hematología y Oncología Pediátricas (SHOP) decided to use the same treatment protocol.

Patients And Method: Pediatric patients diagnosed with B-type non-Hodgkin's lymphoma without a previous history of malignant diseases were eligible for this study. They were classified in 3 groups of risk: group A (resected stage I and abdominal stage II), group B (not eligible for groups A or C), and group C (with central nervous system involvement and L3 leukemia).

Childhood central nervous system tumours--incidence and survival in Europe (1978-1997): report from Automated Childhood Cancer Information System project.

This paper describes the incidence and survival of childhood central nervous system (CNS) tumours in Europe for the period 1978-1997. A total of 19,531 cases, aged 0-14 years, from the ACCIS database were analysed by five regions: the British Isles, East, North, South, and West. Overall age-standardised incidence rate (ASR) of CNS tumours in Europe (1988-1997) was 29.

[Molecular diagnosis of retinoblastoma: molecular epidemiology and genetic counseling].

Background And Objective: Retinoblastoma, a prototype of hereditary cancer, is the most common intraocular tumor in children and a potential cause of blindness from therapeutic eye ablation, second tumors in germ line mutation carriers, and even death when untreated. The molecular scanning of RB1 in search of germ line mutations in 213 retinoblastoma patients from Spain, Cuba, Colombia and Serbia, has led to the detection of 106 mutations whose knowledge is important for genetic counselling and characterization of phenotypic-genotypic relations.

Patients And Method: Mutational study (PCR-sequentiation and microsatellites analysis) in patients with retinoblastoma, from Spain, Cuba, Colombia and Serbia.