The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP.

A specific chromosomal abnormality, t(2;13)(q35;q14), was discovered in five cases of advanced rhabdomyosarcoma. It was identified directly in cells that had metastasized from bone marrow in one patient and in xenografts derived from the tumors of four other patients. The translocation was not restricted by histologic subtype, but was found in cases classified as alveolar, undifferentiated, or embryonal. Cytogenetic hallmarks of gene amplification (double minute chromosomes and homogeneously staining regions) were apparent in three cases. Other frequent abnormalities included rearrangements of chromosome 1p and trisomy of chromosome 8. The absence of the t(2;13) in more than 100 cases of other pediatric solid tumors investigated in our laboratory indicates its specificity for rhabdomyosarcoma. These cytogenetic findings suggest directions for further investigation of the molecular events underlying the genesis of this tumor.

We present complete mitochondrial genomes (mitogenomes) for three orthopterans (Xyleus modestus, Physemacris variolosa, and Ellipes minuta) and describe MOSAS (manipulation, organization, storage, and analysis of sequences), software we developed to facilitate annotation and analysis. We analyze the base composition, start and stop codons, non-coding regions, and gene order among these and 18 other orthopteran mitogenomes from GenBank and reconstruct a phylogeny of Orthoptera. We propose a tetranucleotide start codon for cox1, and hypothesize that the tRNA(Asp)-tRNA(Lys) rearrangement is a synapomorphy for Acridomorpha, but not Caelifera. We further describe MOSAS, user-friendly software we used for this analysis. MOSAS streamlines sequence data storage, organization, annotation, and alignment, and provides convenient search tools for dataset construction and a robust annotation engine particularly suited to annotating mitogenomes (available at http://mosas.byu.edu).

The fusion of villous cytotrophoblasts into the multinucleated syncytiotrophoblast is critical for the essential functions of the mammalian placenta. Using RNA-Seq gene expression and quantitative protein expression, we identified genes and their cognate proteins which are coordinately up- or down-regulated in two cellular models of cytotrophoblast to syncytiotrophoblast development, human primary villous and human BeWo cytotrophoblasts. These include hCGβ, TREML2, PAM, CRIP2, INHA, FLRG, SERPINF1, C17orf96, KRT17 and SAA1. These findings provide avenues for further understanding the mechanisms underlying mammalian placental synctiotrophoblast development.

Infant leukemia (IL) is a rare sporadic cancer with a grim prognosis. While most cases are accompanied by MLL-rearrangements and harbor very few somatic mutations; less is known about the genetics of the cases without MLL translocations. We performed the largest exome sequencing study to date on matched non-cancer DNA from pairs of mothers and IL patients to characterize congenital variation that may contribute to early leukemogenesis. Using the COSMIC database to define acute leukemia-associated candidate genes, we find a significant enrichment of rare, potentially functional congenital variation in IL patients compared to randomly selected genes within the same patients and unaffected pediatric controls. IL AML patients had more overall variation than IL ALL patients, but less of that variation was inherited from mothers. Of our candidate genes, we found that MLL3 was a compound heterozygote in every infant who developed AML and 50% of infants who developed ALL. These data suggest a model by which known genetic mechanisms for leukemogenesis could be disrupted without an abundance of somatic mutation or chromosomal rearrangements. This model would be consistent with existing models for the establishment of leukemia clones in utero and the high rate of IL concordance in monozygotic twins.