title: Absence of Y chromosome in human placental site trophoblastic tumor.
abstract: Placental site trophoblastic tumor is a neoplasm of extravillous intermediate trophoblast at the implantation site, preceded in the majority of cases by a female gestational event. Our pilot investigation suggested that the development of this tumor might require a paternally derived X chromosome and the absence of a Y chromosome. Twenty cases of placental site trophoblastic tumor were included in this study. Genotyping at 15 polymorphic loci and one sex determination locus was performed by multiplex PCR followed by capillary electrophoresis. X chromosome polymorphisms were determined by PCR amplification of exon 1 of the human androgen receptor gene using primers flanking the polymorphic CAG repeats within this region. Genotyping at 15 polymorphic loci was informative and paternal alleles were present in all tumors, confirming the trophoblastic origin of the tumors. The presence of an X chromosome and the absence of a Y chromosome were observed in all tumors. Among 13 cases in which analysis of the X chromosome polymorphism was informative, all but one demonstrated at least two X alleles and seven cases showed one identifiable paternal X allele. These results confirm a unique pathogenetic mechanism in placental site trophoblastic tumor, involving an exclusion of the Y chromosome from the genome and, therefore, a tumor arising from the trophectoderm of a female conceptus. As epigenetic regulations of imprinting during X chromosome inactivation are of significant biological implications, placental site trophoblastic tumor may provide an important model for studying the sex chromosome biology and the proliferative advantage conferred by the paternal X chromosome.
authors.affiliation: Department of Pathology, Yale University, New Haven, CT 06520-8023, USA. pei.hui@yale.edu
authors.forename: Pei
authors.initials: P
authors.lastname: Hui
authors.forename: Hanlin L
authors.initials: HL
authors.lastname: Wang
authors.forename: Peiguo
authors.initials: P
authors.lastname: Chu
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Baergen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sklar
authors.forename: Ximing J
authors.initials: XJ
authors.lastname: Yang
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
mesh_terms: D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D050173:Genes, Y-Linked; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D008297:Male; D010920:Placenta / Q000473:pathology*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D014328:Trophoblastic Neoplasms / Q000235:genetics* / Q000473:pathology; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm