Incidence of NUT carcinoma in Western Australia from 1989 to 2014: a review of pediatric and adolescent cases from Perth Children's Hospital.

Background: NUT carcinoma (NC), previously known as NUT midline carcinoma, is a rare and very aggressive cancer that occurs in both children and adults. NC is largely chemoresistant, with an overall survival of less than 7 months. Because the carcinoma is not restricted to a particular organ, diagnosis is often a challenge.

Atypical nested 22q11.2 duplications between LCR22B and LCR22D are associated with neurodevelopmental phenotypes including autism spectrum disorder with incomplete penetrance.

Background: Chromosome 22q11.2 is susceptible to genomic rearrangements and the most frequently reported involve deletions and duplications between low copy repeats LCR22A to LCR22D. Atypical nested deletions and duplications are rarer and can provide a valuable opportunity to investigate the dosage effects of a smaller subset of genes within the 22q11.

The potential impact of NIPT as a second-tier screen on the outcomes of high-risk pregnancies with rare chromosomal abnormalities.

Aim: To describe the potential impact of using noninvasive prenatal testing (NIPT) as a second-tier test, on the diagnosis and outcomes of pregnancies identified as high risk through first trimester screening (FTS) in a cohort of real pregnancies.

Materials And Methods: Western Australian FTS and diagnostic data (2007-2009) were linked to pregnancy outcomes. Karyotype results from invasive prenatal testing in high-risk women were analysed.

Evaluation of fluorescence in-situ hybridization in monomorphic endometrial stromal neoplasms and their histological mimics: a review of 49 cases.

Aims: To perform a population-based review of monomorphic endometrial stromal tumours and their histological mimics presenting over a 20-year period, including an evaluation of fluorescence in-situ hybridization (FISH) for the JAZF1 and YWHAE breakaparts.

Methods And Results: Forty-nine tumours were examined, comprising 13 histological mimics and 36 endometrial stromal tumours [six stromal nodules (ESNs), 25 low-grade stromal sarcomas (ESSs), and five monomorphic undifferentiated sarcomas (mUESs)]. Nine ESSs showed variant histological patterns, including smooth muscle, sex cord-like/glandular, fibrous or rhabdoid differentiation.

Prenatal screening for Down syndrome in Australia: costs and benefits of current and novel screening strategies.

Objective: To analyse the cost-effectiveness and performance of noninvasive prenatal testing (NIPT) for high-risk pregnancies following first-trimester screening compared with current practice.

Methods: A decision tree analysis was used to compare the costs and benefits of current practice of first-trimester screening with a testing pathway incorporating NIPT. We applied the model to 32 478 singleton pregnancies screened between January 2005 and December 2006, adding Medicare rebate data as a measure of public health system costs.

SNP-based arrays complement classic cytogenetics in the detection of chromosomal aberrations in Wilms' tumor.

Wilms' tumors have characteristic chromosomal abnormalities, such as the 11p13 deletion, in a subset of cases. This is one of the very few reports comparing single nucleotide polymorphism (SNP) array analysis with conventional karyotyping of Wilms' tumors. A total of 43 frozen tumor samples were analyzed using the Affymetrix Cytogenetics Whole-Genome 2.

Structural chromosome disruption of the NR3C2 gene causing pseudohypoaldosteronism type 1 presenting in infancy.

Type I pseudohypoaldosteronism (PHA1) is a rare form of mineralocorticoid resistance presenting in infancy with renal salt wasting and failure to thrive. Here, we present the case of a 6-week-old baby girl who presented with mild hyponatraemia and dehydration with a background of severe failure to thrive. At presentation, urinary sodium was not measurably increased, but plasma aldosterone and renin were increased, and continued to rise during the subsequent week.

Perilobar nephrogenic rests and chromosome 22.

Perilobar nephrogenic rests (NR) are precursor lesions that may display genetic changes similar to their associated Wilms tumor (WT). Two patients presented with WT, both with perilobar NR and 1 with bilateral, multifocal metachronous WT. Both patients' WT displayed monosomy 22 as the predominant cytogenetic change, and the constitutional cytogenetic analysis was normal.

Pathology, genetics and cytogenetics of Wilms' tumour.

Wilms' tumour (WT) is an embryonal cancer of childhood and is thought to be derived from embryonic kidney precursor cells. The Knudson two hit model was initially thought to occur in WT, but findings emerging from genetic and cytogenetic studies in the past two decades have implicated several genetic events. Recent techniques in genetic analysis have improved our ability to characterise changes in genes involved in WT which include WT1, CTNNB1, IGF2 and WTX.

Pre-natal, clonal origin of t(1;11)(p32;q23) acute lymphoblastic leukemia in monozygotic twins.

Aim: Observation of identical genetic changes in leukemia cells from monozygotic twin pairs has provided evidence for the in utero single clonal origin hypothesis of leukemia, with intraplacental metastasis the basis for concordance. Investigation of this rare mixed lineage leukemia (MLL) cytogenetic abnormality aims to provide further evidence of the genetic changes that underpin this aggressive form of leukemia in infants.

Method: The clinical features of a monozygotic infant twin pair with acute lymphoblastic leukemia (ALL) are reported.

Socio-demographic disparities in the uptake of prenatal screening and diagnosis in Western Australia.

Introduction: Since the early 1980s, prenatal screening using ultrasound and biochemical markers has been used to refine the risk of Down syndrome and other fetal anomalies prior to considering fetal karyotyping. The performance of prenatal screening is subject to ongoing monitoring in Western Australia. The collection of these data can also assist in the identification of any potential inequities of access to prenatal screening within the state-wide programme.

Cytogenetic findings in Wilms' tumour: a single institute study.

Aims: Cytogenetic abnormalities of Wilms' tumour (WT) treated in a single institution in Western Australia were reviewed. Correlation with histologic subtypes, stage, presence of nephrogenic rests and age of the patient at diagnosis were also evaluated.

Methods: 53 WT specimens were encountered between 1995 and 2009.

Rate of X chromosome aneuploidy in young fertile women: Comparison of cultured and uncultured cell preparations using fluorescence in situ hybridisation.

Background: X chromosome aneuploidy <10% in female patients is a routinely used reporting limit in diagnostic cytogenetics. X aneuploidy (<10%) is commonly detected in women investigated for infertility or recurrent miscarriages. It is unclear if this aneuploidy is causally relevant or related to the culture process.

The selective use of rapid aneuploidy screening in prenatal diagnosis.

Aims: To evaluate the diagnostic utility and costing of the selective use of rapid aneuploidy screening (RAS) for chorion villus sampling (CVS) and amniocentesis specimens.

Methods: CVS and amniocenteses performed between 2000 and 2006 were identified. Cases were subdivided into two groups: (i) RAS in addition to long-term culture and (ii) long-term chromosome culture alone.

First trimester predictors of adverse pregnancy outcomes.

Aim: To identify first trimester indicators of adverse pregnancy outcomes.

Method: Data were obtained from the statewide evaluation of first trimester screening for Down syndrome in Western Australia which included 22,695 pregnancies screened between August 2001 and October 2003. Screening data were linked with pregnancy outcome information from the Hospital Morbidity Database and the Birth Defects Registry.

Classic and desmoplastic medulloblastoma: complete case reports and characterizations of two new cell lines.

Medulloblastoma (MB) is the most common type of brain tumor affecting children. These tumors are a significant cause of childhood mortality and morbidity, and more effective and less invasive treatment options are urgently required. To achieve these aims, it will be critical to develop a more comprehensive understanding of the molecular pathogenesis of MB.

Clear cell renal cell carcinoma with smooth muscle stroma.

A recent publication described 5 unusual clear cell renal tumors with prominent smooth muscle stroma that were characterized only by immunostaining. We report 3 additional tumors composed of clear cell renal cell carcinoma intimately admixed with abundant smooth muscle stroma. Epithelial differentiation of the malignant clear cell components and smooth muscle differentiation of the benign spindle cell stroma was confirmed by the immunostaining profiles and by electron microscopy.

First-trimester combined screening for Down syndrome and other fetal anomalies.

Objective: This study assessed fetal outcomes for pregnancies identified at increased risk for Down syndrome by first-trimester combined ultrasound examination and maternal serum biochemistry screening.

Methods: First-trimester combined screening data were obtained from ultrasound clinics across Western Australia between August 2001 and October 2003. Prenatal screening data were linked with pregnancy outcome information held in state health database registers using probabilistic record-linkage techniques.

Primary renal synovial sarcoma confirmed by cytogenetic analysis: a lesion distinct from sarcomatoid renal cell carcinoma.

Primary synovial sarcoma rarely originates in the renal parenchyma. When this occurs, origin of this unusual tumor type has been the subject of debate in the literature, with a suggestion that previously reported cases may be more correctly described as renal cell carcinoma with sarcomatoid dedifferentiation. Synovial sarcoma and sarcomatoid renal cell carcinoma may be indistinguishable on pure histologic and immunohistochemical grounds, but these tumors contain distinctly different sets of chromosomal abnormalities.

Detection of hemizygous deletions in genomic DNA from leukaemia specimens for the diagnosis of patients.

Hemizygous deletions in genomic DNA appear to play an important role in tumorigenesis. The loss or inactivation of tumour suppressor genes (TSGs) is of critical importance in most malignancies, and has been shown to affect response to therapy. Here, we report a quantitative real-time polymerase chain reaction (qPCR) designed to detect two TSGs at the CDKN2A locus, p16(INK4A) and p14(ARF) that allows the detection of hemizygous deletions.

An investigation into sub-telomeric deletions of chromosome 22 and pervasive developmental disorders.

Deletions of the sub-telomeric region of chromosome 22 have been associated with mental retardation, developmental delay, and autistic behaviors. This study investigated sub-telomeric anomalies of chromosome 22 using fluorescent in situ hybridization (FISH) probes in 82 subjects diagnosed with autism and atypical autism. No microdeletions were detected in this group.

Gene expression profiles in a panel of childhood leukemia cell lines mirror critical features of the disease.

The development of new drugs against cancer requires established cell lines. They are needed for in vitro studies to identify candidate drugs and in xenograft models to measure drug efficacy in vivo. Specific criteria need to be fulfilled by cell lines used in the evaluation of potential novel therapeutic agents.