Y chromosome loss and rearrangement in non‐small‐cell lung cancer

Abstract

While loss of the Y chromosome from the karyotype of tumor cells has frequently been found in a number of human malignancies of different types, structural alterations are a much less common finding. Prompted by the high frequency of cytogenetic Y chromosome loss found in primary non-small-cell lung cancer (NSCLC), and the fact that NSCLC karyotypes usually contain marker chromosomes of unidentified origin, we have determined the Y chromosome status of 12 NSCLC samples (7 cell lines and 5 primary tumors) at a molecular level. Of the 9 cases which did not have a cytogenetically detectable Y chromosome, 4 were negative for all the Y sequences tested. The other 5, in contrast, retained some Y chromosome sequences. In 1 case (H520), only Yq heterochromatic sequences were detected, whereas in the remaining 4 (L162, L93, L125 and L71) both Yq heterochromatic sequences and Y euchromatic sequences were retained. The region of common overlap for loss of Y euchromatin was Yp distal to the Y centromere. We hypothesize that deletion of Yp sequences may play a role in tumor progression in NSCLC due to loss of a tumor-suppressor gene.

The Human Y Chromosome: The Biological Role of a “Functional Wasteland”

“…Y chromosome loss and rearrangements have been associated with different types of cancer, such as bladder cancer (Sauter et al [51]), male sex cord stroma tumours (de Graaff et al [52]), lung cancer (Center et al [53]) and esophageal carcinoma (Hunter et al [54]). Although loss and rearrangements of this chromosome are relatively frequent in different types of cancer, there is no direct evidence for a role of Y in tumour progression since no proto-oncogenes, tumour suppresser genes or mismatch repair genes have been localised to the Y chromosome.…”

Y chromosome haplotypes and testicular cancer in the English population

“…6 Spermatogenic dysfunction is more common than can be explained by either local tumour or general cancer effect, since patients with other malignant diseases have normal, or only slightly decreased, semen quality. 7 Human Y chromosome loss and rearrangements have been associated with specific types of cancer, such as bladder cancer, male sex cord stromal tumours, lung cancer, and oesophageal carcinoma, [8][9][10][11] suggesting that both oncogenes and tumour suppressor genes exist on this chromosome. A number of Y chromosome genes, or gene families, appear to be necessary for male germ cell development and maintenance 12 13 and are candidates for involvement in oncogenesis of male specific cancers.…”

Y-chromosome status identification suggests a recipient origin of posttransplant non–small cell lung carcinomas: chromogenic in situ hybridization analysis

“…Y-CISH testing showed complete lack of Y-chromosome signals, and thus, the tumor was interpreted as of a recipient origin. Because Y-chromosome loss is not uncommon in NSCLC [21,22], it lays ground for false-positive Y-CISH results where lack of Y-chromosome signals is a sign of cytogenetic alterations and not a female sex. Complete absence of Y-chromosome would be more in keeping with a female sex, as was seen in our case; however, additional studies may be needed to confirm the Y-CISH assessment in male to female transplants.…”