Nonrandom cell-cycle timing of a somatic chromosomal translocation: The t(X;17) of alveolar soft-part sarcoma occurs in G2.
The cell-cycle timing of somatic chromosomal translocations in cancer remains poorly understood but may be relevant to their etiology and the mechanism of their formation. Alveolar soft-part sarcoma (ASPS) is a rare malignant soft-tissue tumor of uncertain lineage that provides an opportunity to address this question. The great majority of ASPSs have relatively simple near-diploid karyotypes characterized by an unbalanced der(17)t(X;17)(p11.2;q25), resulting in nonreciprocal fusion of TFE3 with ASPSCR1 (a.k.a. ASPL), with consequent net gain of Xp11.2-->pter and loss of 17q25-->qter. The presence of a normal X along with the der(17)t(X;17) in ASPSs that occur in men has been well described in previous cytogenetic reports and is most readily explained by a translocation in the G2 phase of the cell cycle. To establish whether formation in G2 is a general feature of the t(X;17), we examined polymorphic loci in Xp11.2-->qter in ASPS from 9 women, including 7 with an unbalanced t(X;17). Our analysis showed that all 7 displayed retention of heterozygosity at all informative markers on Xp11.2-->qter, supporting preferential formation of the t(X;17) in the G2 phase of the cell cycle. Given that the two derivative chromosomes of a translocation in G2 would be expected to segregate together half the time, the predominance of an unbalanced der(17)t(X;17) also raises the possibility of a selective advantage in ASPS cells for gain of Xp11.2-->pter or loss of 17q25.3-->qter or retention of an active copy of TFE3.
Huang
Hsuan-Ying
HY
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Lui
Man Yee
MY
Ladanyi
Marc
M
D000293:Adolescent; D000328:Adult; D002648:Child; D002886:Chromosomes, Human, Pair 17; D041321:Chromosomes, Human, X; D005260:Female; D016195:G2 Phase; D006801:Humans; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic