A case of chronic myeloid leukemia with Philadelphia chromosome variant

En 5-10% de los casos de Leucemia Mieloide Crónica (LMC), el cromosoma Philadelphia (Ph1) se origina como producto de translocaciones variantes (Ph1 variante). Estas últimas involucran otros autosomas además del 9 y 22 clásicamente implicados. Se presenta aquí un caso de LMC cuyo cromosoma Ph1 variante fue originado a partir de una translocación compleja que involucró los cromosomas 3, 9 y 22 [t(3;9;22)(p21,q34;q11)]. El análisis mediante FISH sugiere un mecanismo de formación en una etapa única, mientras el análisis por RT-PCR mostró la presencia del rearreglo molecular BCR/ABL1 correspondiente a la isoforma p210. El paciente no presentó variaciones significativas en los parámetros de respuesta clínica (respuesta hematológica, respuesta citogenética y respuesta molecular) respecto de aquellos pacientes con el Ph1 estándar.Among the CML there is a fraction of cases (5–10%) in which the Philadelphia chromosome (Ph1) originates from variant translocations (Ph1 variant), in which there are autosomes involved other than the classic 9 and 22. Here we report a case of CML where a variant Ph1 chromosome was originated from a complex translocation involving chromosomes 3, 9 and 22 [t(3,9,22)(p21,q34,q11)]. FISH analysis suggests that the mechanism of translocation occurred in a single step. Furthermore, the RT-PCR analysis also showed the presence of the classical molecular rearrangement corresponding to the BCR/ABL1 p210 isoform. The patient showed no significant variations in the parameters of clinical response (hematologic, cytogenetic, and molecular response) from those patients carrying a standard Ph1 chromosome.Fil: Gutierrez, Leandro German. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; ArgentinaFil: Dos Santos, Patricia Carolina. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Rolón, Amada. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; ArgentinaFil: Melnichuk, Ana M.. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; ArgentinaFil: Argüelles, Carina F.. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; ArgentinaFil: Fenocchio, Alberto Sergio. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Citogenética y Genética Humana; Argentin

Pursuit of Gene Fusions in Daily Practice: Evidence from Real-World Data in Wild-Type and Microsatellite Instable Patients

Agnostic biomarkers such as gene fusions allow to address cancer patients to targeted therapies; however, the low prevalence of these alterations across common malignancies poses challenges and needs a feasible and sensitive diagnostic process. RNA-based targeted next generation sequencing was performed on 125 samples of patients affected either by colorectal carcinoma, melanoma, or lung adenocarcinoma lacking genetic alterations in canonical driver genes, or by a colorectal carcinoma with microsatellite instability. Gene fusion rates were compared with in silico data from MSKCC datasets. For NTRK gene fusion detection we also employed a multitarget qRT-PCR and pan-TRK immunohistochemistry. Gene fusions were detected in 7/55 microsatellite instable colorectal carcinomas (12.73%), and in 4/70 of the “gene driver free” population (5.71%: 3/28 melanomas, 10.7%, and 1/12 lung adenocarcinomas, 8.3%). Fusion rates were significantly higher compared with the microsatellite stable and “gene driver positive” MSKCC cohorts. Pan-TRK immunohistochemistry showed 100% sensitivity, 91.7% specificity, and the occurrence of heterogeneous and/or subtle staining patterns. The enrichment of gene fusions in this “real-world” cohort highlights the feasibility of a workflow applicable in clinical practice. The heterogeneous expression in NTRK fusion positive tumours unveils challenging patterns to recognize and raises questions on the effective translation of the chimeric protein

Cytogenetic description of Bunocephalus doriae Boulenger, 1902 (Siluriformes: Aspredinidae) from the Paraná River (Misiones, Argentina)

In this work, Bunocephalus doriae was cytogenetically analyzed. A karyotype with a diploid number of 2n= 50 comprising 6m, 10sm, 6st, and 28a (FN= 72) chromosomes was observed. The occurrence of an asymmetric karyotype with a large number of acrocentric chromosomes distinguishes this species from others the Order Siluriformes. An exclusive character observed is the first pair of subtelocentric as the largest chromosome pair of the complement. NORs detected using AgNO3 were located in the terminal regions, on the short arm of a subtelocentric chromosome pair (pair 11), in a secondary constriction. C-banding revealed heterochromatic centromeric regions on several chromosomes of the complement after C-banding. This is the first cytogenetic description of this species and the first cytogenetic report on a member of the family Aspredinidae

Cytogenetic analyses in three species of Moenkhausia Eigenmann, 1903 (Characiformes, Characidae) from Upper Paraná River (Misiones, Argentina)

Moenkhausia Eigenmann, 1903 is one of the most diverse genera within Characidae, being an important component of the Neotropical fish fauna. Three members of this genus were cytogenetically analyzed: M. dichroura Kner, 1858, M. intermedia Eigenmann, 1908 and M. sanctaefilomenae Steindachner, 1907. The three species showed 2n = 50 bi-armed chromosomes (NF = 100) and different karyotype formulas: 22m + 22sm + 6st in M. dichroura, 16m + 28sm + 6st in M. intermedia, and 12m + 32sm + 6st in M. sanctaefilomenae. In addition, supernumerary chromosomes (or B-chromosomes) were detected in M. intermedia and M. sanctaefilomenae. C-positive bands were restricted to pericentromeric regions, secondary constrictions and supernumerary chromosomes. Active nucleolus organizer regions (Ag-NORs) and positive CMA3 bands were observed in a single pair of sm chromosomes. Pericentromeric DAPI positive signals were evidenced on chromosomes of M. sanctaefilomenae only. Overall, the three species showed a conservative karyotype macrostructure (diploid number, number of chromosome arms) and variations in microstructure (karyotype formulas, presence/absence of supernumerary chromosomes). We discuss how the observed differences could have been shaped.Fil: Sánchez, Kevin Imanol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Takagui, Fabio H.. Universidade Estadual de Londrina; BrasilFil: Fenocchio, Alberto Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Universidad Nacional de Misiones. Instituto de Biología Subtropical; Argentin