Novel germline TRAF3IP3 mutation in a dyad with familial acute B lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, representing 25% of all new cancer diagnoses. Advances in genomic sequencing have demonstrated that inherited genetic risk factors play a larger role in leukemia development than previously appreciated. AIM: We identified a father-daughter dyad with childhood B-cell ALL and aimed to investigate whether the pair shared a gene associated with leukemia predisposition. METHODS: We performed whole exome sequencing on their leukemia and germline samples and RNA-seq on their leukemia samples. RESULTS: We discovered a novel germline chromosomal structural variant in chromosome 1q32.2 within the TRAF3IP3 gene. TRAF3IP3 regulates B-cell lymphopoiesis, and this mutation likely resulted in a predisposition to leukemia by causing expansion of immature B-cell precursors which are highly vulnerable to secondary somatic mutations. Based on the lack of concordance in the somatic mutational profiles between this dyad's leukemia samples, we suspect that the acquired somatic mutations rather than this germline mutation are what dictated their leukemia phenotypes, which we confirmed through RNA-seq by comparing to sporadic cases of B-cell ALL. CONCLUSION: This research may have identified a novel gene involved in leukemogenesis which may also be involved in de novo cases of ALL. Additional studies are needed to further characterize this TRAF3IP3 structural variant, the co-occurring somatic mutations within these leukemia samples and their combined role in leukemogenesis.

En bloc resection of a C-1 lateral mass osteosarcoma: technical note.

Osteosarcoma is an aggressive primary bone tumor. It is currently treated with multimodality therapy including en bloc resection, which has been demonstrated to confer a survival benefit over intralesional resection. The authors present the case of an 8-year-old girl with a C-1 lateral mass osteosarcoma, which was treated with a 4-stage en bloc resection and spinal reconstruction. While technically complex, the feasibility of en bloc resection for spinal osteosarcoma should be explored in the pediatric population.

NORMATIVE STANDARDS AND PATTERNING OF FAT AND MUSCLE IN WHITE AND BLACK NEWBORN INFANTS.

Due to the lack of normative data in newborns, we report fat and muscle patterning, and standards for the sums of fat and muscle areas and muscle circumferences for arm, forearm, thigh, and calf in white and black newborn infants that may have clinical application in the assessment of body composition in newborns. Significant differences were found between white males and white females in fatness patterning: white female newborns were larger for all 21 variables except height. Statistically significant differences (t test; p < 0.05) existed for five skinfold measurements (forearm, subscapular, suprailiac, thigh, medial calf), three limb fat areas (forearm, thigh, calf), and the sums of the skinfolds and fat areas despite similar limb circumferences. Black female newborns were larger than black males for five of the eight skinfolds (with a significant difference observed in medial calf skinfold), for all of the limb fat areas, and for the sums of the skinfolds and fat areas. Despite their larger skinfolds and fat areas, black females had smaller circumferences. No sex-related trends or significantly different variables were observed in the muscle patterning of white infants. Differences in muscle patterning were observed between black males and black females, with males having larger values for all 14 variables. Statistically significant differences were found between white and black infants, with white newborns having greater height, medial calf skinfold, and calf fat area.

NORMATIVE STANDARDS AND COMPARISON OF ANTHROPOMETRIC DATA OF WHITE AND BLACK NEWBORN INFANTS.

We report normative standards for length, weight, 17 craniofacial dimensions, 5 hand and foot measurements, 7 circumferences, 9 skinfold thicknesses, penile length, and testicular volume in black and white newborns. No significant differences in these variables were found between black males and females. White males had greatest craniofacial height, head length, head breadth, minimum frontal diameter, bizygomatic diameter, and head circumference, whereas white females had largest medial calf, thigh, forearm, and subscapular skinfolds. White infants had largest weight, head circumference, head length, head breadth, calf and chest circumferences, and medial calf and forearm skinfolds, whereas nose breadth, mouth breadth, and penile length were greatest in black newborns.