RESUMO
Multiple myeloma (MM), is a heterogeneous disease in which chromosomal abnormalities are important for prognostic risk stratification. Cytogenetic profiling with FISH on plasma cells from bone marrow samples (BM-PCs) is the current gold standard, but variable infiltration of plasma cells or failed aspiration can hamper this process. Ultra-low coverage sequencing (ULCS) of circulating cell-free DNA (ccfDNA) may offer a minimally invasive alternative for the work-up of these cases. We compared ULCS, aCGH and FISH on selected BM-PCs in a routine setting with ULCS of ccfDNA for the detection of somatic copy number aberrations (CNAs) in MM. METHODS: Purified CD138+ BM-PCs of 23 MM patients at initiation of their treatment were subjected to aCGH, FISH and ULCS. Paired samples of peripheral blood-ccfDNA obtained at diagnosis were analyzed by ULCS and compared to the results found in BM-PCs. RESULTS: Using ULCS of ccfDNA, cytogenetic markers were identified in 18 out of 23 patients; five cases could not be analyzed due to low (≤3%) tumor fraction (TF). High similarity between CNA profiles of BM-PCs and ccfDNA was found. Moreover, 78% of the ccfDNA profiles resulted in the same risk classification as the routine FISH and/or BM-PCs ULCS and aCGH. Chromothripsis was detected in five patients; these had the highest TF values (range 7.1% to 42%) in our series and their profiles showed other high-risk anomalies. CONCLUSION: This proof-of-principle study indicates that ULCS of ccfDNA can reveal CNAs in MM and should be explored further as a cost-efficient alternative, especially in cases where BM-PC purification fails.
Assuntos
Ácidos Nucleicos Livres , Mieloma Múltiplo/genética , Sequenciamento Completo do Genoma , Medula Óssea , Variações do Número de Cópias de DNA , Humanos , Hibridização in Situ Fluorescente , PlasmócitosRESUMO
To the authors' best knowledge, this is the first report of acute myeloid leukemia (AML) detected by noninvasive prenatal testing. This was an aggressive case that otherwise would have been difficult to characterize due to disadvantages of "gold-standard" techniques.
RESUMO
El género Lagothrix se encuentra representado en Colombia por Lagothrix lagothricha lagothricha y Lagothrix lagothricha lugens y siendo un género llamativo para el tráfico y caza, se han realizado varios trabajos encaminados a conocer sobre su ecología y ciclo de vida mostrando la importancia de este género en el ecosistema aunque sus características citogenéticas no han sido bien estudiadas. En este trabajo se analizaron 18 individuos (seis, L. l. lugens y 12 L. L. lagothricha) en cautiverio provenientes de zoológicos y centros de rescate, en los que por medio de técnicas de cultivo de sangre periférica y bandaje cromosómico G, C, R, Q y NOR se determinó un cariotipo estándar de 2n=62 para todos los individuos con dos variantes de éste también conocidos como cariomorfos que se originan por la diferencia en su número fundamental (NF), debido a una inversión pericéntrica en el par cromosómico 24. Dentro de estos cariomorfos se encontraron polimorfismos en varios pares cromosómicos que no fueron determinantes para diferenciar subespecies en los individuos trabajados, por lo que se recomienda revisar la taxonomía del género.
The genus Lagothrix is represented in Colombia by Lagothrix lagothricha lagothricha and Lagothrix lagothricha lugens but their cytogenetic features have not been well characterized. We studied 18 captive individuals (6, L. l. lugens and 12, L. L. lagothricha) from zoos and rescue centers, using techniques of peripheral blood culture and G, C, R, Q and NOR chromosome banding. We determined the standard karyotype 2n = 62 for all analyzed individuals with two karyotype variants (also known as karyomorphs) that showed different fundamental numbers due to a pericentric inversion on chromosome pair 24. Within these karyomorphs other polymorphisms were found in several pairs that were not crucial to distinguishing subspecies. We recommend reviewing the taxonomy of the genus especially at the subspecies level.
