A complex rearrangement between APC and TP63 associated with familial adenomatous polyposis identified by multimodal genomic analysis: a case report

Genetic testing of the APC gene by sequencing analysis and MLPA is available across commercial laboratories for the definitive genetic diagnosis of familial adenomatous polyposis (FAP). However, some genetic alterations are difficult to detect using conventional analyses. Here, we report a case of a complex genomic APC-TP63 rearrangement, which was identified in a patient with FAP by a series of genomic analyses, including multigene panel testing, chromosomal analyses, and long-read sequencing. A woman in her thirties was diagnosed with FAP due to multiple polyps in her colon and underwent total colectomy. Subsequent examination revealed fundic gland polyposis. No family history suggesting FAP was noted except for a first-degree relative with desmoid fibromatosis. The conventional APC gene testing was performed by her former doctor, but no pathogenic variant was detected, except for 2 variants of unknown significance. The patient was referred to our hospital for further genetic analysis. After obtaining informed consent in genetic counseling, we conducted a multigene panel analysis. As insertion of a part of the TP63 sequence was detected within exon16 of APC, further analyses, including chromosomal analysis and long-read sequencing, were performed and a complex translocation between chromosomes 3 and 5 containing several breakpoints in TP63 and APC was identified. No phenotype associated with TP63 pathogenic variants, such as split-hand/foot malformation (SHFM) or ectrodactyly, ectodermal dysplasia, or cleft lip/palate syndrome (EEC) was identified in the patient or her relatives. Multimodal genomic analyses should be considered in cases where no pathogenic germline variants are detected by conventional genetic testing despite an evident medical or family history of hereditary cancer syndromes

Artificially Induced Epithelial-Mesenchymal Transition in Surgical Subjects: Its Implications in Clinical and Basic Cancer Research

BACKGROUND: Surgical samples have long been used as important subjects for cancer research. In accordance with an increase of neoadjuvant therapy, biopsy samples have recently become imperative for cancer transcriptome. On the other hand, both biopsy and surgical samples are available for expression profiling for predicting clinical outcome by adjuvant therapy; however, it is still unclear whether surgical sample expression profiles are useful for prediction via biopsy samples, because little has been done about comparative gene expression profiling between the two kinds of samples. METHODOLOGY AND FINDINGS: A total of 166 samples (77 biopsy and 89 surgical) of normal and malignant lesions of the esophagus were analyzed by microarrays. Gene expression profiles were compared between biopsy and surgical samples. Artificially induced epithelial-mesenchymal transition (aiEMT) was found in the surgical samples, and also occurred in mouse esophageal epithelial cell layers under an ischemic condition. Identification of clinically significant subgroups was thought to be disrupted by the disorder of the expression profile through this aiEMT. CONCLUSION AND SIGNIFICANCE: This study will evoke the fundamental misinterpretation including underestimation of the prognostic evaluation power of markers by overestimation of EMT IN past cancer research, and will furnish some advice for the near future as follows: 1) Understanding how long the tissues were under an ischemic condition. 2) Prevalence of biopsy samples for in vivo expression profiling with low biases on basic and clinical research. 3) Checking cancer cell contents and normal- or necrotic-tissue contamination in biopsy samples for prevalence

CAVEOLIN-3 IS UP-REGULATED IN THE PHYSIOLOGICAL LEFT VENTRICULAR HYPERTROPHY INDUCED BY VOLUNTARY EXERCISE TRAINING IN RATS

Various substances have been introduced in relation with cardiac hypertrophy almost always with controversy in their roles in signal transduction. Those controversies may attribute to the diversity of cardiac hypertrophy. We previously showed that calcineurin was activated in physiological left ventricular hypertrophy (LVH) induced by voluntary exercise training, but not in decompensated pressure-overload LVH. In the current study, we advanced our search for the differences between the voluntary exercise-induced LVH and the pressure-overload LVH into several other hypertrophy-related substances including caveolin. Wistar rats were assigned to one of the following three groups: 10 weeks of voluntary exercise (EX), sedentary regimen (SED), and 4 weeks of ascending aortic constriction (AC). The EX rats voluntarily ran 1.6±1.1 km/day in the specially manufactured cages resulting in LVH (24 % increase in left ventricular weight per body weight ratio). Myocardial tissue homogenate of the EX rats revealed different characteristics in signal transduction of hypertrophy from that of the AC. The EX rats had normal sarcoplasmic reticulum (SR) Ca2+ATPase mRNA level and normal myosin heavy chain isozyme pattern assessed by RNA protection assay, while AC rats had decreased SR Ca2+ATPase mRNA level and increased beta myosin heavy chain mRNA level. Myocardial caveolin-3 protein levels assessed by Western blotting increased in the EX rats but decreased in the AC rats. The voluntary exercise-induced LVH differed in signal transduction from the decompensated pressure-overload LVH. Caveolin-3 was induced in the voluntary exercise-induced LVH, while it was decreased in the decompensated pressure-overload LV

Pulse-mode measurement of electron beam halo using diamond-based detector

Using a diamond-based detector, the electron beam halo in a high-energy accelerator can be measured with a lower detection limit than that using other instruments, such as a core monitor, a dose meter, or an optical fiber. We have successfully measured an electron beam halo using diamond-based detectors operating in the ionization mode, which were installed in the beam duct to measure the intensity of the beam halo directly. Pulse-by-pulse measurements were adopted to suppress the background noise efficiently. Feasibility tests on the diamond-based detector and beam halo monitor were performed in the beam dump area of the 8 GeV SPring-8 synchrotron booster and at the 250 MeV SPring-8 Compact SASE Source test accelerator for the SPring-8 Angstrom Compact free electron LAser (SACLA), respectively. We achieved a lower detection limit of 2×10^{3}  electrons/pulse for single-shot measurement, which corresponds to a ratio of about 10^{-6} relative to the typical charge of the beam core of 0.3 pC. We also confirmed the feasibility of the electron beam halo monitor for use as an interlock sensor to protect undulator permanent magnets used in SACLA from radiation damage

Przypadek przejściowego bloku przedsionkowo-komorowego z przewodzeniem 2:1, który ustąpił po suplementacji tyroksyną zastosowaną w celu leczenia subklinicznej postaci niedoczynności tarczycy

Mężczyznę w wieku 42 lat przyjęto do szpitala, w którym pracują autorzy niniejszego doniesienia, z powodu napadów kołatania serca. W holterowskim badaniu EKG wykazano blok przedsionkowo-komorowy (AV) z przewodzeniem 2:1 oraz bradykardię z minimalną częstością akcji serca wynoszącą 44 uderzenia/min. Stwierdzono obecność wskazań do przeprowadzenia dalszych badań elektrofizjologicznych oraz do wszczepienia rozrusznika serca. Wyniki badań laboratoryjnych wykonanych w dniu przyjęcia wykazały podwyższone stężenie tyreotropiny przy prawidłowym stężeniu tyroksyny. W celu wykluczenia czynnościowego bloku AV przez 2 tygodnie podawano pacjentowi tyroksynę, zaś w holterowskim badaniu EKG wykonanym po tym okresie wykazano znaczącą poprawę częstości akcji serca bez obecności bloku AV lub długotrwałych przerw w przewodzeniu. Na tej podstawie uznano, że ciężka bradykardia oraz blok AV z przewodzeniem 2:1 wynikały z subklinicznej postaci niedoczynności tarczycy, a przyjmowanie tyroksyny całkowicie wyeliminowało istniejące objawy. (Folia Cardiologica Excerpta 2006; 1: 448-451