Microchimeric Cells, Sex Chromosome Aneuploidies and Cancer

Abstract

The phenomenon of feta-maternal microchimerisms inspires numerous questions. Many questions remain to be answered regarding this new avenue of genetics. The X and Y chromosomes have been associated with malignancy in different types of human tumors. We aimed to investigate the numerical aberrations of chromosomes X and Y in lung cancer (LC) and bladder cancer (BC) and review recent evidence for possible roles of microchimeric cells (McCs) in these cancers. We carried out cytogenetic analysis of the tumor and blood sampling in 52 cases of people with BC and LC, and also with 30 healthy people. A total of 48 (92.3 %) of the patients revealed sex chromosome aneuploidies (SCAs). A total SCAs was found in 9.8 % of 2282 cells that were analyzed as one or more cells in each case. The 68 and 95 SCAs were found in the 1952 (8.4 %) cells in peripheral blood, and 41 and 19 SCAs in the 330 (18.2 %) cells in the tumoral tissues respectively. There was a significant difference in the frequencies of SCAs between the patients and the control groups determined by the Fischer's Exact Test (p < 0.0001). The frequencies of SCAs were higher in the tumoral tissues than in the blood (p < 0.0001). There was a significant difference in the frequencies of SCAs between the tumor and blood tissues, and this was higher in the tumor tissue (p < 0.0001). In general, 78.9 % (41) of the 52 patients with LC and BC had X and Y chromosome monosomies. Largely a Y chromosome loss was present in 77.8 % of the men, and the 47, XXY karyotype was found in 33.3 % of them. The second most common SCA was monosomy X, and was found in 71.4 % of the women. McCs were observed in 26.9 % of the 52 patients, and the frequencies of McCs were higher in the blood than in the tissues (p < 0.0001). XY cells were identified in the lung and bladder tissues of the women who had been pregnant with boys, but not in those who had not. There was a significant difference in the frequencies of McCs between the LC and BC patients (p < 0.0005). We speculate that the microchimerism could have a general beneficial role in cancer, in which some sites may not be evident because of an allogeneic maternal immune reaction that hastens cancer development. A further understanding of McCs may help in anticipating its implications in cancer. Our results may suggest that SCAs may be contributing factors in the development of LC and BC, and aneuploidies of X and Y chromosomes play a role in the pathogenesis of cancers.

Loss of Y Chromosome in Peripheral Blood of Colorectal and Prostate Cancer Patients

“…The mean Y/X ratios were significantly lower in colorectal patients than prostate cancer patients. The higher percentage of patients with LOY in our cohort of cancer patients is consistent with the recent findings showing significantly increased frequency of sex chromosomes monosomies in patients with lung and bladder cancer in comparison to healthy controls [ 33 ].…”

Y Chromosome Loss Is a Frequent Event in Barrett’s Adenocarcinoma and Associated with Poor Outcome

“…LoY is known to be the most common acquired mutation in healthy males with a rising prevalence with age and is found in up to 20% of men older than 80 years [ 39 ]. For colorectal, prostate, bladder and lung cancer studies showed a significant higher frequency of LoY in blood cells compared to healthy controls [ 40 , 41 ]. A further limitation is that the high frequency of LoY in fully developed EAC does not explain the gender specificity of the tumor, as the Y chromosome status in Barrett´s mucosa without dysplasia has not been analyzed in large cohorts yet [ 20 , 42 , 43 ].…”

El problema de la pérdida de Y. Revisión de la literatura

“…Al revisar el papel de los cromosomas sexuales en los carcinomas de pulmón y vejiga en 52 hombres y mujeres con dichos tumores y un grupo control de 30 casos sin neoplasias (28) , se encontró LOY en 77,8% de los hombres y LOX en 71,4% de las mujeres con neoplasia. Los autores concluyeron que las anomalías de cromosomas sexuales pueden ser factores contribuyentes a la patogenia del cáncer.…”

“…Si hay un mosaicismo 45 X/46 XX, la severidad de las anomalías dependerá del porcentaje de células con pérdida del X. En estos casos se encuentra las anomalías anatómicas características (síndrome de Turner), incluyendo trastornos de la función reproductiva y desarrollo de neoplasias (28) . En el caso de los procesos patológicos del adulto, en relación con LOY, y que se ha resumido, se plantea que estarían en relación con un defecto en el sistema de inmunovigilancia.…”