Background: Alveolar soft-part sarcoma (ASPS) is a rare malignant soft tissue tumor with both clinically and morphologically distinct features. It often involves the extremities of adolescents and young adults and shows a predilection for females. Recently, ASPS was found to have a nonreciprocal der(17)t(X;17) translocation with the corresponding fusion gene located in chromosome 17. Because females have an extra X-chromosome, their likelihood of developing an X;autosome translocation is theoretically double that of males, and thus, this extra X-chromosome is a likely explanation for female predominance of ASPS.
Methods: The authors used data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry program, which included 87 ASPS cases (33 males and 54 females), and published ASPS cases, which included 317 cases (121 males and 196 females), to test our hypothesis. The authors compared the observed proportion of female cases with that expected under the two X-chromosomes-double-risk hypothesis including the consideration of X-inactivation status.
Results: The hypothesis that the fusion gene is not subject to X-inactivation is supported by data (P = 0.6, 0.24, and 0.20 for SEER cases, published cases, and their combination, respectively). In contrast, the competing hypothesis that the fusion gene is subject to X-inactivation is rejected (P = 0.007, < 0.00001, and < 0.00001 for SEER cases, published cases, and their combination, respectively).
Conclusions: Therefore, the authors found a statistical association between the female predominance observed in ASPS and female possession of an extra X-chromosome/noninactivation of the ASPS X;autosome translocation fusion gene.