Carcinosarcoma of the parotid gland: a case report and review of the literature.

Background: Carcinosarcoma of the parotid gland is an extremely rare malignancy comprising of 0.04-0.16% of all salivary gland tumors.

Application of modern autoradiography to nuclear forensic analysis.

Modern autoradiography techniques based on phosphorimaging technology using image plates (IPs) and digital scanning can identify heterogeneities in activity distributions and reveal material properties, serving to inform subsequent analyses. Here, we have adopted these advantages for applications in nuclear forensics, the technical analysis of radioactive or nuclear materials found outside of legal control to provide data related to provenance, production history, and trafficking route for the materials. IP autoradiography is a relatively simple, non-destructive method for sample characterization that records an image reflecting the relative intensity of alpha and beta emissions from a two-dimensional surface.

TGF-β reduces DNA ds-break repair mechanisms to heighten genetic diversity and adaptability of CD44+/CD24- cancer cells.

Many lines of evidence have indicated that both genetic and non-genetic determinants can contribute to intra-tumor heterogeneity and influence cancer outcomes. Among the best described sub-population of cancer cells generated by non-genetic mechanisms are cells characterized by a CD44+/CD24- cell surface marker profile. Here, we report that human CD44+/CD24- cancer cells are genetically highly unstable because of intrinsic defects in their DNA-repair capabilities.

A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs.

Purpose: The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported.

Patients And Methods: We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system.

Accuracy and risk of malignancy for diagnostic categories in urine cytology at a large tertiary institution.

Background: At a high-volume center, it became necessary to provide benchmarks for the accuracy and risk of malignancy per urine cytology diagnostic category. The additive sensitivity for the determination of the residual risk of disease was calculated with the goal of determining the performance of cytology and optimal triage, including the number of urine samples, before the detection of malignancy in surveillance patients.

Methods: A 2-year laboratory information system-based search was conducted, and it yielded 587 subjects (695 biopsy and cytology pairs) with histological follow-up.

Chimeric negative regulation of p14ARF and TBX1 by a t(9;22) translocation associated with melanoma, deafness, and DNA repair deficiency.

Melanoma is the most deadly form of skin cancer and DiGeorge syndrome (DGS) is the most frequent interstitial deletion syndrome. We characterized a novel balanced t(9;22)(p21;q11.2) translocation in a patient with melanoma, DNA repair deficiency, and features of DGS including deafness and malformed inner ears.

Massively-parallel sequencing of genes on a single chromosome: a comparison of solution hybrid selection and flow sorting.

Background: Targeted capture, combined with massively-parallel sequencing, is a powerful technique that allows investigation of specific portions of the genome for less cost than whole genome sequencing. Several methods have been developed, and improvements have resulted in commercial products targeting the human or mouse exonic regions (the exome). In some cases it is desirable to custom-target other regions of the genome, either to reduce the amount of sequence that is targeted or to capture regions that are not targeted by commercial kits.

AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations.

Cancer-initiating translocations such as those associated with lymphomas require the formation of paired DNA double-strand breaks (DSBs). Activation-induced cytidine deaminase (AID) produces widespread somatic mutation in mature B cells; however, the extent of "off-target" DSB formation and its role in translocation-associated malignancy is unknown. Here, we show that deregulated expression of AID causes widespread genome instability, which alone is insufficient to induce B cell lymphoma; transformation requires concomitant loss of the tumor suppressor p53.

Therapeutic vulnerability of an in vivo model of alveolar soft part sarcoma (ASPS) to antiangiogenic therapy.

In vivo growth of alveolar soft part sarcoma (ASPS) was achieved using subcutaneous xenografts in sex-matched nonobese diabetic severe combined immunodeficiency mice. One tumor, currently at passage 6, has been maintained in vivo for 32 months and has maintained characteristics consistent with those of the original ASPS tumor including (1) tumor histology and staining with periodic acid Schiff/diastase, (2) the presence of the ASPL-TFE3 type 1 fusion transcript, (3) nuclear staining with antibodies to the ASPL-TFE3 type 1 fusion protein, (4) maintenance of the t(X;17)(p11;q25) translocation characteristic of ASPS, (5) stable expression of signature ASPS gene transcripts and finally, the development and maintenance of a functional vascular network, a hallmark of ASPS. The ASPS xenograft tumor vasculature encompassing nests of ASPS cells is highly reactive to antibodies against the endothelial antigen CD34 and is readily accessible to intravenously administered fluorescein isothiocyanate-dextran.

Porphyrin-based photocatalytic nanolithography: a new fabrication tool for protein arrays.

Nanoarray fabrication is a multidisciplinary endeavor encompassing materials science, chemical engineering, and biology. We formed nanoarrays via a new technique, porphyrin-based photocatalytic nanolithography. The nanoarrays, with controlled features as small as 200 nm, exhibited regularly ordered patterns and may be appropriate for (a) rapid and parallel proteomics screening of immobilized biomolecules, (b) protein-protein interactions, and/or (c) biophysical and molecular biology studies involving spatially dictated ligand placement.

Changes of higher order chromatin arrangements during major genome activation in bovine preimplantation embryos.

Gene-dense chromosome territories (CTs) are typically located more interior, gene-poor CTs more peripheral in mammalian cell nuclei. Here, we show that this gene-density correlated CT positioning holds for the most gene-rich and gene-poor bovine chromosomes 19 and 20, respectively, in bovine fibroblast and lymphocyte nuclei. In order to determine the period at which this non-random CT order is established during development, we performed fluorescence in situ hybridization, on three-dimensionally preserved bovine preimplantation embryos generated by in vitro fertilization and investigated the distribution of BTA 19 and 20 CTs.

Phototocatalytic lithography of poly(propylene sulfide) block copolymers: toward high-throughput nanolithography for biomolecular arraying applications.

Photocatalytic lithography (PCL) is an inexpensive, fast, and robust method of oxidizing surface chemical moieties to produce patterned substrates. This technique has utility in basic biological research as well as various biochip applications. We report on porphyrin-based PCL for patterning poly(propylene sulfide) block copolymer films on gold substrates on the micrometer and submicrometer scales.

Phylogenomic analysis by chromosome sorting and painting.

Chromosome sorting by flow cytometry is the principle source of chromosome-specific DNA not only for chromosome painting, but also for many other types of genomic analysis such as library construction, discovery and isolation of genes, chromosome specific direct DNA selection, and array painting. Chromosome sorting coupled with chromosome painting is a rapid method for global phylogenomic comparisons. These two techniques have made notable contributions to our knowledge of the evolution of the mammalian genome.

A de novo apparently balanced translocation [46,XY,t(2;9)(p13;p24)] interrupting RAB11FIP5 identifies a potential candidate gene for autism spectrum disorder.

Autism spectrum disorder (ASD) is a severe developmental disorder of the central nervous system characterized by impairments in social interaction, communication, and range of interests and behaviors. The syndrome's prevalence is estimated to be as high as 1 in 150 American children yet its etiology remains largely unknown. Examination of observed cytogenetic variants in individuals with ASD may identify genes involved in its pathogenesis.

Porphyrin-based photocatalytic lithography.

Photocatalytic lithography couples light with photoreactive coated mask materials to pattern surface chemistry. We excite porphyrins to create radical species that photocatalytically oxidize, and thereby pattern, chemistries in the local vicinity. The technique advantageously is suited for use with a wide variety of substrates.

The ancestral carnivore karyotype (2n = 38) lives today in ringtails.

Chromosome painting was used to investigate the conservation of high-resolution longitudinal 4',6-diamidino-2-phenylindole (DAPI)/G bands in Carnivore chromosomes. Cat (Felis catus) and raccoon dog (Nyctereutes procyonoides) painting probes were hybridized to the ringtail (Bassaricus astutus), dwarf mongoose (Helogale parvula), and Malagasy civet (Fossa fossa) to identify homologous chromosome elements. The patterns of chromosome segment homology among Carnivore species allowed us to reconstruct and propose the disposition of a high-resolution banded ancestral carnivore karyotype (ACK).

Multidirectional cross-species painting illuminates the history of karyotypic evolution in Perissodactyla.

The order Perissodactyla, the group of odd-toed ungulates, includes three extant families: Equidae, Tapiridae, and Rhinocerotidae. The extremely rapid karyotypic diversification in perissodactyls has so far prevented the establishment of genome-wide homology maps between these three families by traditional cytogenetic approaches. Here we report the first genome-wide comparative chromosome maps of African rhinoceroses, four tapir species, four equine species, and humans.

Phylogenomics of species from four genera of New World monkeys by flow sorting and reciprocal chromosome painting.

Background: The taxonomic and phylogenetic relationships of New World monkeys (Platyrrhini) are difficult to distinguish on the basis of morphology and because diagnostic fossils are rare. Recently, molecular data have led to a radical revision of the traditional taxonomy and phylogeny of these primates. Here we examine new hypotheses of platyrrhine evolutionary relationships by reciprocal chromosome painting after chromosome flow sorting of species belonging to four genera of platyrrhines included in the Cebidae family: Callithrix argentata (silvered-marmoset), Cebuella pygmaea (pygmy marmoset), Callimico goeldii (Goeldi's marmoset) and Saimiri sciureus (squirrel monkey).

Chromosome painting in the manatee supports Afrotheria and Paenungulata.

Background: Sirenia (manatees, dugongs and Stellar's sea cow) have no evolutionary relationship with other marine mammals, despite similarities in adaptations and body shape. Recent phylogenomic results place Sirenia in Afrotheria and with elephants and rock hyraxes in Paenungulata. Sirenia and Hyracoidea are the two afrotherian orders as yet unstudied by comparative molecular cytogenetics.

Molecular evidence for species-level distinctions in clouded leopards.

Among the 37 living species of Felidae, the clouded leopard (Neofelis nebulosa) is generally classified as a monotypic genus basal to the Panthera lineage of great cats. This secretive, mid-sized (16-23 kg) carnivore, now severely endangered, is traditionally subdivided into four southeast Asian subspecies (Figure 1A). We used molecular genetic methods to re-evaluate subspecies partitions and to quantify patterns of population genetic variation among 109 clouded leopards of known geographic origin (Figure 1A, Tables S1 ans S2 in the Supplemental Data available online).

The ancestral eutherian karyotype is present in Xenarthra.

Molecular studies have led recently to the proposal of a new super-ordinal arrangement of the 18 extant Eutherian orders. From the four proposed super-orders, Afrotheria and Xenarthra were considered the most basal. Chromosome-painting studies with human probes in these two mammalian groups are thus key in the quest to establish the ancestral Eutherian karyotype.

A high-grade uterine leiomyosarcoma with human chorionic gonadotropin production.

Ectopic human chorionic gonadotropin production has been described in a wide variety of non-germ cell tumors, particularly in epithelial tumors, but rarely in sarcomas. In this report, we describe the case of 49-year-old woman with a history of "uterine fibroids," who presented with vaginal bleeding and a positive urine pregnancy test. After pregnancy was ruled out by ultrasound, the patient underwent a laparotomy and hysterectomy for a presumptive diagnosis of "fibroids" and was found to have carcinomatosis at the time of the surgery.

Molecular cytogenetics discards polyploidy in mammals.

Polyploidy, the presence of more than two chromosome sets, is common in plants, but extremely rare in animals. The absence of polyploid organisms with well-differentiated sex chromosomes suggests that the disruption of the dosage between autosomes and sex chromosomes is incompatible with normal development. Thus, the announcement in 1999 of tetraploidy in a mammal, the South American red vizcacha rat Tympanoctomys barrerae, provoked great interest, even though the definitive proof of tetraploidy, the presence of four copies of each chromosome, was never provided.

A chromosome painting test of the basal eutherian karyotype.

We studied the chromosomes of an Afrotherian species, the short-eared elephant shrew Macroscelides proboscideus with traditional banding techniques and mapped the homology to human chromosomes by in-situ hybridization of human chromosome paints. Here we present for the first time the karyotype of this species, including banding patterns. The chromosome painting allowed us to test various hypotheses of the ancestral Eutherian karyotype, the validity of the radical taxonomic assemblage known as Afrotheria and the phylogenetic position of the elephant shrew within the Afrotheria.