HGG-34. DETECTION OF ONCOGENIC FUSION EVENTS IN SUPRATENTORIAL GLIOBLASTOMAS OF YOUNG CHILDREN

Abstract INTRODUCTION Glioblastoma in infancy and early childhood is characterized by a more favorable outcome compared to older children, a stable genome, and the occurrence of tyrosine kinase gene fusions that may represent therapeutic targets. METHODS 50 glioblastomas (GBM) with supratentorial location occurring in children younger than four years were retrieved from the archives of the Brain Tumor Reference Center, Institute of Neuropathology, University of Bonn. DNA and RNA were extracted from FFPE tumor samples. Gene fusions were identified by FISH using break-apart probes for ALK, NTRK1, -2, -3, ROS1 and MET, Molecular Inversion Probe (MIP) methodology, and targeted RNA sequencing. RESULTS 37 supratentorial GBM occurred in the first year of life, 13 GBM between one and four years. 18 cases showed fusions of ALK to different fusion partners; all occurred in the first year of life (18/37 cases, 48.6%). Fusions of ROS1 were found in 5, MET in 3, NTRK1, -2, -3 in 10 cases. 12 cases showed no and two novel fusions. The different methods led to comparable results; targeted RNA sequencing was not successful in a fraction of cases. Break-apart FISH led to reliable results on the next day, MIP technology represented the most sensitive method for analysis of FFPE samples. CONCLUSIONS Gene fusions involving the tyrosine kinase genes ALK, MET, ROS1 and NTRK1, -2, -3 occurred in 72% of glioblastomas of children younger than four years; the most frequent were ALK fusions occurring in infant GBM. DNA based MIP technology represented the most robust and sensitive assay.

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HGG-28. ONCOGENIC TYROSINE KINASE GENE FUSIONS IN SUPRATENTORIAL HIGH GRADE GLIOMAS OF YOUNG CHILDREN - COMPARISON OF RNA- AND DNA-BASED METHODS FOR THEIR RELIABLE DETECTION

Neuro-Oncology ◽

10.1093/neuonc/noab090.092 ◽

2021 ◽

Vol 23 (Supplement_1) ◽

pp. i23-i23

Author(s):

Torsten Pietsch ◽

Gerrit Gielen ◽

Andreas Waha ◽

Evelyn Doerner ◽

Andre O von Bueren ◽

...

Keyword(s):

Young Children ◽

Tyrosine Kinase ◽

Rna Sequencing ◽

First Year ◽

High Grade ◽

Gene Fusions ◽

Kinase Gene ◽

Tyrosine Kinase Gene ◽

First Year Of Life ◽

Rna And Dna

Abstract High-grade diffuse gliomas in early childhood are characterized by a more favorable outcome compared to older children. We have shown in previous studies that these tumors are characterized by stable genomes. The occurrence of tyrosine kinase gene fusions in high-grade gliomas of infancy may represent therapeutic targets. 50 glioblastomas (GBM) with supratentorial location occurring in children younger than four years were retrieved from the archives of the Brain Tumor Reference Center, Institute of Neuropathology, Bonn University. DNA and RNA were extracted from FFPE tumor samples. Gene fusions were identified on the DNA level by FISH using break-apart probes for ALK, NTRK1, -2, -3, ROS1 and MET and Molecular Inversion Probe (MIP) methodology. On the RNA level, fusion transcripts were detected by targeted RNA sequencing as well as Nanostring assay with fusion-specific probes. 37 supratentorial GBM occurred in the first year of life, 13 GBM between one and four years. 18 cases showed fusions of ALK to different partners; all occurred in the first year of life (18/37, 48.6%). Fusions of ROS1 were found in 5, MET in 3, NTRK1, -2, -3 in 10 cases. 12 cases showed no and two cases novel fusions. The different methods led to comparable results. Only recurrent fusions with known fusion partners were detectable with fusion sequence-specific Nanostring probes and library construction for targeted RNA sequencing failed in a fraction of cases. Break-apart FISH led to reliable results on the next day, and MIP technology represented the most sensitive method for analysis of FFPE samples. Gene fusions involving the tyrosine kinase genes ALK, MET, ROS1 and NTRK1, -2, -3 occurred in 72% of glioblastomas of young children; most frequent were ALK fusions occurring in infant GBM. DNA-based MIP technology represented the most robust and sensitive assay. A combination of RNA- and DNA-based methods to detect these fusions with high reliability is recommended.

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Targetable kinase gene fusions in high-risk B-ALL: a study from the Children’s Oncology Group

Blood ◽

10.1182/blood-2016-12-758979 ◽

2017 ◽

Vol 129 (25) ◽

pp. 3352-3361 ◽

Cited By ~ 108

Author(s):

Shalini C. Reshmi ◽

Richard C. Harvey ◽

Kathryn G. Roberts ◽

Eileen Stonerock ◽

Amy Smith ◽

...

Keyword(s):

High Risk ◽

Tyrosine Kinase ◽

Effective Treatment ◽

Pediatric Patients ◽

Genetic Alterations ◽

Gene Fusions ◽

Oncology Group ◽

Kinase Gene ◽

Tyrosine Kinase Signaling ◽

Key Points

Key Points Ph-like ALL is characterized by a diverse array of genetic alterations activating cytokine receptor and tyrosine kinase signaling. Pediatric patients with Ph-like ALL can be identified in real time for effective treatment stratification.

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ACUTE POLIOMYELITIS IN INFANTS UNDER ONE YEAR OF AGE: EPIDEMIOLOGICAL AND CLINICAL FEATURES

PEDIATRICS ◽

10.1542/peds.16.4.478 ◽

1955 ◽

Vol 16 (4) ◽

pp. 478-488

Author(s):

Harold Abramson ◽

Morris Greenberg

Keyword(s):

New York ◽

Clinical Features ◽

Sugar Content ◽

Case Fatality ◽

Paralytic Poliomyelitis ◽

First Year ◽

Older Children ◽

One Year ◽

First Year Of Life ◽

Acute Poliomyelitis

In order to compare the epidemiological and clinical features of poliomyelitis in infants under 1 year with those in children and adults, a study was made of all cases of poliomyelitis that occurred in New York City in 1949 and 1950. This revealed the following characteristics of the disease among infants in the first year of life: Clinically recognizable poliomyelitis was of infrequent occurrence among infants under 1 year of age. It was even more infrequent among infants in the first 6 months of life. This is in marked contrast to the findings in the 1950 epidemic in Israel, where one-third of all cases occurred in the first year of life, and one-tenth in infants in the first half year of life. Male infants exhibited a greater susceptibility to the disease than females. Fatalities in this age group were high, particularly among infants under 3 months, with some predominance of deaths in males. Under 1 year of age, non-paralytic poliomyelitis was unusual, especially in the first 6 months of life. Paralytic forms of the disorder were dominant, spinal involvement being more common than bulbar. Case fatality occurred chiefly in bulbar forms of the disease, as in older children and adults. The fatality rate was higher than in older children and higher than in all ages combined. The onset of poliomyelitis among infants under 1 year of age was variable. It was acute, with fever, or fever with nuchal spasm, or the triad of fever, nuchal spasm and spasm of back muscles. Temperature at onset of illness averaged 98.3°F.(36.8°C.), with a low of 97.6°F.(36.3°C.), and a high of 102°F.(38.8°C.). Temperatures recorded subsequently during the day of onset of illness were from 99.9°F. (37.7°C.) to 105°F.(40.5°C.), the mean being 102.8°F. (39.3°C.). The interval between onset of illness and first detection of paralysis averaged 5.5 days, with a spread from the day of onset to 25 days later. Paralysis of a single limb occurred more frequently than of 2 or more limbs, and the ratio of arm to leg paralysis was about 1 to 3. Initial spinal punctures in infants under 1 year were made on an average of 3.4 days after onset of illness in non-paralytic cases, and 5.7 days in paralytic cases. The spinal fluid was usually clear, with a mean count of 91 lymphocytes/mm. . The average sugar content was 55 mg./and protein 72 mg./100 ml. of fluid.

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STUDIES IN SICKLE CELL ANEMIA

PEDIATRICS ◽

10.1542/peds.14.3.209 ◽

1954 ◽

Vol 14 (3) ◽

pp. 209-214

Author(s):

ROLAND B. SCOTT ◽

LELABELLE C. FREEMAN ◽

ANGELLA D. FERGUSON

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Sickle Cell Trait ◽

Age Groups ◽

Test Group ◽

Progressive Increase ◽

First Year ◽

Older Children ◽

Low Incidence ◽

First Year Of Life

This survey of 1100 Negro children in various age categories was undertaken to determine the effect of age upon the appearance of the sickling phenomenon from infancy throughout childhood. The general incidence of sickling in 1100 Negro children including sickle cell anemia and sickle cell trait was 7.4%. The data on the incidence of the asymptomatic sickling trait and of sickle cell anemia are summarized by age and sex in Tables I and II. We encountered 22 cases of sickle anemia, seven of which were previously undiagnosed and unknown. Sixteen cases of sickle cell anemia in males and six in females were encountered in the total test group, comprising 651 males and 449 females. This investigation disclosed 60 subjects bearing the asymptomatic sickling trait. There were 40 and 20 instances of asymptomatic sickling observed in 635 males and 443 females, respectively. When the sexes were divided into two age categories (1 month through 4 years and 5 years through 16 years), there was an actual decrease in the incidence of sickling in the girls and an increase in the sickling phenomenon in the boys. We have no explanation for this finding. The overall incidence of the sickling trait for both sexes in all age groups represents no significant deviation from a 1:1 ratio. The data available from this study failed to disclose a definite progressive increase in the incidence of sickling in the age groups studied. Quantitatively the general transition from the low incidence of sickling in the newborn (3.4%) to the higher occurrence in older children (7.5%) apparently takes place during the first year of life. Additional studies of both a qualitative and quantitative nature and involving a detailed age breakdown during the first year of life would probably elucidate this period of transition.

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Characteristics of Child Battering in Hong Kong: A Controlled Study

The British Journal of Psychiatry ◽

10.1192/bjp.142.1.89 ◽

1983 ◽

Vol 142 (1) ◽

pp. 89-94 ◽

Cited By ~ 23

Author(s):

F. Lieh-Mak ◽

S. Y. Chung ◽

Y. W. Liu

Keyword(s):

Hong Kong ◽

Social Class ◽

Psychiatric Disorder ◽

Unwanted Pregnancy ◽

Cultural Factors ◽

Controlled Study ◽

Control Group ◽

First Year ◽

Older Children ◽

First Year Of Life

SummaryThe characteristics in Hong Kong of 37 cases of child battering and their families compared to a control group matched for age of child and social class of family revealed that the families of battered children had significantly more problems, with a higher prevalence of psychiatric disorder among the parents. The victims were usually the product of unwanted pregnancy and had been separated from their parents in the first year of life. In Hong Kong older children rather than infants were at risk of being battered. The cultural factors in operation are discussed.

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Cranial vault remodeling for sagittal craniosynostosis in older children

Neurosurgical FOCUS ◽

10.3171/2011.5.focus1196 ◽

2011 ◽

Vol 31 (2) ◽

pp. E3 ◽

Cited By ~ 13

Author(s):

S. Alex Rottgers ◽

Peter D. Kim ◽

Anand Raj Kumar ◽

James J. Cray ◽

Joseph E. Losee ◽

...

Keyword(s):

Retrospective Chart Review ◽

Cranial Vault ◽

First Year ◽

Older Children ◽

Sagittal Craniosynostosis ◽

Calvarial Defects ◽

Clinically Significant ◽

First Year Of Life ◽

Cranial Vault Remodeling

Object Sagittal craniosynostosis is the most common form of craniosynostosis and is commonly treated within the first year of life. Optimal treatment of patients older than 1 year of age is not well characterized. The authors reviewed cases of sagittal craniosynostosis involving patients who were treated surgically at their institution when they were older than 1 year in order to determine the rate of intracranial hypertension (ICH), potential to develop nonhealing cranial defects, and the need for various surgical procedures to treat the more mature phenotype. Methods A retrospective chart review was conducted of all cases in the Children's Hospital of Pittsburgh Neurosurgery Database involving patients who underwent cranial vault remodeling for scaphocephaly after 1 year of age between October 2000 and December 2010. Results Ten patients were identified who met the inclusion criteria. Five patients underwent anterior two-thirds cranial vault remodeling procedures, 3 patients underwent posterior vault remodeling, and 2 patients underwent 2-staged total vault remodeling. All patients had improved head shapes, and mean cephalic indices improved from 65.4 to 69.1 (p = 0.05). Six patients exhibited signs of ICH. No patients with more than 3 months of follow-up exhibited palpable calvarial defects. Conclusions Patients with sagittal synostosis treated after 1 year of age demonstrate increased rates of ICH, warranting diligent evaluations and surveillance to detect it; rarely develop clinically significant cranial defects if appropriate bone grafting is performed at the time of surgery; and achieve acceptable improvements in head shape.

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