Tetraploidy in hydatidiform moles

STUDY QUESTION: How does tetraploidy develop in hydatidiform moles (HMs), and what is the frequency of the different origins?

SUMMARY ANSWER: Most molar pregnancies with tetraploid cells appear to be produced by somatic endoreduplications, while a minority originate from a tetraploid zygote. The frequency of zygotic tetraploidy was estimated to be 0.7%.

WHAT IS KNOWN ALREADY: The parental origin of the genome in tetraploid HMs has only been evaluated in a few cases, most showing three genome sets from the father (PPPM). Estimates of the proportion of HMs that are tetraploid vary between 2 and 28%.

STUDY DESIGN, SIZE, DURATION: From 1986 to 2010, unfixed samples of clinically suspected molar pregnancies were forwarded to the Danish Mole Project. For this cohort study 442 samples fulfilled the following criteria for inclusion: macroscopic appearance of HM and ≥ 10 vesicular chorionic villi with a diameter of ≥ 1 mm.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Of 403 karyotyped samples, 21 cases disclosed ≥ 2 tetraploid metaphases. The 21 cases were scrutinized by karyotyping, flow cytometry (FC) and DNA-marker analysis.

MAIN RESULTS AND THE ROLE OF CHANCE: Among 20 HMs, 3 showed the genotype PPPM: one with the sex chromosomes XXYY and two with XXXY, indicating that they originated in tetraploid zygotes. In 14 androgenetic, one likely androgenetic and two mosaics, the tetraploid cells likely developed by endoreduplications of diploid cells. One case did not fulfil the histopathological criteria for HM.

LIMITATIONS, REASONS FOR CAUTION: As an inclusion criterion was the macroscopic observation of vesicular chorionic villi, some non-molar hydropic placentas may have been included and some early moles may have been excluded.

WIDER IMPLICATIONS OF THE FINDINGS: In future, studies to determine that an HM is tetraploid and discriminate cases of mosaicism and to deduce the origin of the tetraploidy must use the techniques of karyotyping, DNA-marker analysis and FC in combination.