A new, automated, four-colour interphase FISH approach for the simultaneous detection of specific aneuploidies of diagnosis and prognosis significance in high hyperdiploid ALL

In hyperdiploid acute lymphoblastic leukaemia (ALL), the simultaneous occurrence of specific aneuploidies confers a more favourable outcome than hyperdiploidy alone. Interphase (I) FISH complements conventional cytogenetics (CC) through its sensitivity and ability to detect chromosome aberrations in non-dividing cells. To overcome the limits of manual I-FISH, we developed an automated four-colour I-FISH approach and assessed its ability to detect concurrent aneuploidies in ALL. I-FISH was performed using centromeric probes for chromosomes 4, 6, 10 and 17. Parameters established for automatic nucleus selection and signal detection were evaluated (3 controls). Cut-off values were determined (10 controls, 1000 nuclei/case). Combinations of aneuploidies were considered relevant when each aneuploidy was individually significant. Results obtained in 10 ALL patients (1500 nuclei/patient) were compared with those by CC. Various combinations of aneuploidies were identified. All clones detected by CC were observed by I-FISH. I-FISH revealed numerous additional abnormal clones, ranging between 0.1 % and 31.6%, based on the large number of nuclei evaluated. Four-colour automated I-FISH permits the identification of concurrent aneuploidies of prognostic significance in hyperdiploid ALL. Large numbers of cells can be analysed rapidly by this method. Owing to its high sensitivity, the method provides a powerful tool for the detection of small abnormal clones at diagnosis and during follow up. Compared to CC, it generates a more detailed cytogenetic picture, the biological and clinical significance of which merits further evaluation. Once optimised for a given set of probes, the system can be easily adapted for other probe combinations

Guidelines for genomic array analysis in acquired haematological neoplastic disorders.

Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single-nucleotide polymorphism-detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test. However, comprehensive and readable presentation of frequently identified complex genomic profiles remains challenging. To assist diagnostic laboratories, standardization and minimum criteria for clinical interpretation and reporting of acquired genomic abnormalities detected through arrays in neoplastic disorders are presented. © 2016 Wiley Periodicals, Inc

Detection rate and localization of prostate cancer recurrence using Ga-PSMA-11 PET/MRI in patients with low PSA values ≤ 0.5 ng/ml

A first analysis of simultaneous Ga-PSMA-11 PET/MRI showed some improvement in the detection of recurrent disease at low serum prostate specific antigen (PSA) values below 0.5 ng/ml compared to the already high detection rate of Ga-PSMA-11 PET/CT. We therefore focused on all patients with biochemical recurrence (BR) and PSA values ≤ 0.5 ng/ml to assess the detection rate for Ga-PSMA-11 PET/MRI. We retrospectively analyzed a cohort of 66 consecutive patients who underwent a Ga-PSMA-11 PET/MRI for BR with a PSA value ≤ 0.5 ng/ml at our institution. Median PSA level was 0.23 ng/ml (range: 0.03 - 0.5 ng/ml). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones or visceral organs was recorded. In addition, all scans with Ga-PSMA-11 PET/MRI positive lesions were retrospectively assessed to analyze if lesions were detected inside or outside of a standard salvage radiotherapy volume. Overall, in 36 of 66 patients (54.5%) PSMA-positive lesions were detected; in 26 of 40 (65%) patients with a PSA between 0.2 - 0.5 ng/ml and in 10 of 26 (38.5%) patients with a PSA < 0.2 ng/ml. Even at those low PSA values, only 8 of 66 (12.1%) patients had exclusive local recurrence. In 23 patients lymph nodes and in 5 patients bone metastases were detected on Ga-PSMA-11 PET/MRI. In 26 of 66 patients (39.4%) PSMA-positive lesions were located outside a standard salvage radiotherapy volume. Our data confirm that Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer, even at low PSA levels ≤ 0.5 ng/ml. In addition, we show that Ga-PSMA-11 PET/MRI detected PSMA-positive lesions outside a standard salvage radiotherapy volume in 39.4% of all patients

Amplification of the G allele at SNP rs6983267 in 8q24 amplicons in myeloid malignancies as cause of the lack of MYC overexpression?

status: publishe