ARTICLE 1 – research

ALT-EJ GENERA REARREGLOS CROMOSÓMICOS EN RESPUESTA A ETOPÓSIDO EN CÉLULAS HUMANAS CON LOS PRINCIPALES SISTEMAS DE REPARACIÓN DE RUPTURAS DE DOBLE CADENA COMPROMETIDOS
ALT-EJ ORIGINATES CHROMOSOMAL REARRANGEMENTS IN RESPONSE TO ETOPOSIDE IN HUMAN CELLS WITH THE MAIN DNA DOUBLE-STRAND BREAK REPAIR SYSTEMS COMPROMISED

Kramar J., Palmitelli M., De Campos-Nebel M., González-Cid M.

The antitumor drug Etoposide (ETO) induces DNA double-strand breaks (DSB) and is associated with the development of secondary neoplasms in treated patients. DSB are repaired by two main mechanisms, homologous recombination (HR) and classical non-homologous end joining (c-NHEJ). When HR and c-NHEJ are defective, DSB are repaired by the PARP-1-dependent alternative end-joining (alt-EJ) pathway. The involvement of alt-EJ in the progression of DSB induced by ETO in the G2 phase of human cells was analyzed. HeLa cells deficient in HR (cohesin RAD21 inhibition, HeLa RAD21kd) and their non-silencing control (HeLa NS) were established. Cells were treated with ETO in the presence of a chemical inhibitor of DNA-PKcs (DNA-PKi, c-NHEJ). In both cell lines, ETO-induced DSB (γH2AX+) in G2 phase were increased compared to their controls. The incorrect repair of DSB in DNA-PKcs- and RAD21-deficient cells caused a synergistic augment in chromatid exchanges and dicentric chromosomes in the first and second metaphase, respectively. In contrast, the frequency of dicentric chromosomes was reduced in PARP-1-deficient cells (HeLa PARP-1kd) following ETO treatment. In HeLa RAD21kd binucleated cells, DNA-PKi/ETO increased the percentage of cells with ≥20 γH2AX foci in the G1-postmitotic phase and of micronuclei at 96 h. A greater accumulation in G2/M was observed in HeLa NS treated with DNA-PKi/ETO compared with HeLa RAD21kd at 8 h. The cell cycle restarted in HeLa NS at 16 h; however, the G2/M accumulation was maintained in HeLa RAD21kd. Chromosomal rearrangements obtained when DNA-PKcs and RAD21 were absent and their decrease in HeLa PARP-1kd cells suggest that alt-EJ contributes to their formation.

Key words: chromosomal aberrations, cell cycle, cohesin, double-strand breaks, DNA repair pathways
Language: Spanish

ARTICLE 2 – research

PRENATALLY DIAGNOSED PARTIAL TRISOMY 3Q22.2→3QTER,
PARTIAL MONOSOMY 11Q25→11QTER AND INTERSTITIAL DELETION
10Q25.1-10Q25.2: A CASE REPORT AND REVIEW OF LITERATURE
DIAGNÓSTICO PRENATAL DE TRISOMÍA PARCIAL 3Q22.2→3QTER, MONOSOMÍA PARCIAL 11Q25→11QTER Y DELECIÓN INTERSTICIAL
10Q25.1-10Q25.2: REPORTE DE UN CASO Y REVISIÓN DE LA LITERATURA

Della Vedova M.C., Gancia M.D., Mendoza G.V., Barrasa N.F., Bravo R., Losada D., Siewert S., Marsá S.M.

A 19-year-old pregnant woman was admitted to our ultrasound department at 20.4 weeks of gestation. Prenatal sonography identified a fetus with trigonocephaly, an omphalocele protruding out of the abdominal wall, on the right side of the umbilical cord, that contained the liver and bowel, claw hand and bot foot. Amniocentesis revealed an unbalanced chromosome constitution 46,XX,der(11)t(3,11)(q22.2,q24.3) resulting in a deletion of 11q24.3 to 11qter and a duplication of 3q22.2 to 3qter product of a “de novo imbalanced translocation”; the parents’ karyotypes were normal. The chromosome microarray results for the proband revealed a 63.07 Mb duplication in the chromosome 3 located at 3q22.2 to terminal 3q29; a 4.08 Mb deletion in the chromosome 11 located at 11q25, and a 5.66 Mb loss in the chromosome 10 located at 10q25.1 to 10q25.2. To the best of our knowledge, this is the first report of this combination of chromosomal abnormalities.

Key words: amniocentesis, chromosome microarray, deletion 10q, deletion 11q, duplication 3q.
Language: English

ARTICLE 3 – review

MICROSOMÍA CRANEOFACIAL, UN RECUENTO ACTUALIZADO
CRANEOFACIAL MICROSOMIA, AN UPDATED REVIEW

Valencia-Pérez A., Quintero-Orozco M.

Craniofacial microsomia (CFM) is a complex congenital condition that affects approximately one in 5,000 live births. It was initially described by Carl Ferdinand Von Arlt in 1881, and over time, various synonymous terms have been used to refer to this condition. The pathophysiology of CFM revolves around the disruption of embryonic craniofacial development, primarily stemming from abnormalities in the first and second pharyngeal arches. Both genetic and non-genetic factors play a role in impacting the development of the ear and jaw. These factors encompass a range of elements, including: variants of transcription factors responsible for neural crest cell migration and patterning, chromatin modifiers, growth factors and their receptors, DNA pre-replication complexes, ribosome assembly, and the spliceosome. Although there is currently a better understanding of the pathophysiology of this entity, it is still necessary to continue with more specific research on the related etiological factors. The aim of this review is to compile the most pertinent genetic factors associated with craniofacial microsomia as reported in the last decade.

Key words: Craneofacial Microsomial, CFM, Genetic Factors, Hemifacial Microsomia, Pharyngeal Arch
Language: Spanish

ARTICLE 4 – review

OMICS: A NEW VISION FOR BREAST CANCER TREATMENT
OMICS: UNA NUEVA VISIÓN DEL TRATAMIENTO DEL CÁNCER DE MAMA

Salvatierra A., Díaz-Baena D., Güven Ö., Ruiz-Serrano E.

Breast cancer is an extremely heterogeneous disease with diverse morphologies, molecular characteristics, and clinical behaviour whose causes include interactions of both genetic and environmental factors. Currently, more than 2,261,419 cases and 684,996 deaths are reported each year worldwide and although great strides have been made, available treatments are inadequate for its most intractable forms. Therefore, knowing the associated molecular bases is essential to improve the prognosis and survival. The omics are high performance technologies utilized to quantify cellular components at a large scale. In this regard, this article presents genomic, epigenomic, transcriptomic, and proteomic research on breast cancer, in an attempt to understand and identify potential therapeutic molecular targets.

Key words: breast cancer, genomics, epigenomics, nutrigenomics, transcriptomics, proteomics, metabolomics
Language: English

ARTICLE 5 – review

HUMAN X-CROMOSOME NON-CODING VARIATION IN LATIN AMERICAN POPULATIONS: A REVIEW
VARIACIÓN NO CODIFICANTE DEL CROMOSOMA X HUMANO EN POBLACIONES LATINOAMERICANAS: UNA REVISIÓN

Catanesi C.I., Hohl D.M., Bolzán A.D.

The human X-chromosome non-coding markers, such as short tandem repeats (STRs), single nucleotide polymorphisms (SNPs), insertion-deletions (INDELs) and Alu insertions, are useful for revealing relationships among populations and for the identification of individuals. In the last decades, a number of studies have been performed to determine the genetic structure of Latin American populations by using X-chromosome markers. These studies provided useful information regarding the genetic composition of these populations and their relationship with Native American, Asian and European populations. One of the most interesting findings achieved by X-chromosome studies is the bias in the sex ratio of individuals that gave rise to the current Latin American populations, as it was previously observed through the analysis of uniparental markers, and which is undoubtedly evidenced in the differential inheritance of X-chromosome in comparison to autosomes. Besides, the genetic drift process that affected Native American populations is more pronounced in X-chromosome markers than in autosomes. The present review summarizes our current knowledge concerning X-chromosome non-coding polymorphisms studied in Latin American populations. 

Key words: genetic diversity, INDEL, SNP, STR, Alu insertion
Language: English

OBITUARY

Dra. LILIANA AMELIA PICARDI
1942-2023