X-chromosomal inactivation skewing in blood cells is associated with early development of lung / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the relationship between skewed X-chromosomal inactivation (SXCI) and development of lung cancer in females.</p><p><b>METHODS</b>DNA was isolated from peripheral blood cells from patients with primary lung cancer (n = 148) and control subjects (n =289). Exon 1 of androgen receptor ( AR) gene was amplified, with its products from different alleles resolved on denaturing polyacrylamide gels and visualized by silver staining. The corrected ratio (CR) between products from different AR alleles before and after Hpa II pretreatment was calculated. All statistical tests were two-sided.</p><p><b>RESULTS</b>With CR> or = 10 adopted as the criterion, SXCI was found more frequently in the younger patients ( C50 years; 7. 9%) than in the controls of the same age group (1. 2% ; P = 0. 046). The SXCI frequency, however, were not significantly different between the old patients ( > 50 years; 4. 5% ) and the controls of the same age group (5. 4% ; P =0. 488). Whether taking CR> or =3 or CR> or =10 as the criteria, the average ages of the patients with SXCI were more than 10 years younger than those without SXCI (P < 0. 05).</p><p><b>CONCLUSION</b>SXCI in blood cells is associated with early development of lung cancer in females.</p>

X-chromosome inactivation patterns of different tumor nodules in multiple leiomyomas of uterus / 中华病理学杂志

<p><b>OBJECTIVE</b>To describe the relationship among different tumor nodules in multiple leiomyomas of uterus.</p><p><b>METHODS</b>Genomic DNA was extracted from fresh tissue samples, digested through incubation with methylation-sensitive Hha I or Hpa II, and amplified via PCR for androgen receptor (AR) and phosphoglycerate kinase (PGK) genes. The length polymorphism on AR gene was demonstrated by denaturing polyacrylamide gel electrophoresis and silver staining, the PGK gene products were treated with Bst XI and resolved on agarose gels.</p><p><b>RESULTS</b>112 cases of leiomyomas and one case of leiomyosarcoma were examined, 89% showing the length polymorphism for AR gene and 30% carrying the polymorphic Bst XI site at PGK locus. Loss of X-chromosome inactivation mosaicism was observed in all the 321 tumor nodules examined from 77 cases, reflecting their clonal cellular composition. The relationship between different nodules was evaluated by their X-chromosome inactivation patterns in the 295 tumor nodules taken from 57 multiple leiomyomas. Similar inactivated alleles were found in all nodules in 30, in most nodules in 7 cases, similar to a multi-nodular leiomyosarcoma, while 20 cases showed near-random distribution of the inactivated alleles in different nodules, indicating their multicentric origins. No relevance was found between this difference and any histopathological parameters including number of mitotic figures and occurrence of bizarre nuclei and degeneration. In addition, an identical mutation and loss of heterozygosity were found at the AR locus in two apparently discrete tumor nodules in one case, providing further evidence for the unicellular origin of these lesions.</p><p><b>CONCLUSIONS</b>The multi-nodular leiomyomas may be classified into multicentric, unicentric types, as well as a mixed type. It remains to be clarified whether different nodules in the unicentric cases originate from a parent tumor by migration or by spreading.</p>