Triploidy—Observations in 154 Diandric Cases

<div><p>Hydatidiform moles (HMs) are abnormal human pregnancies with vesicular chorionic villi, imposing two clinical challenges; miscarriage and a risk of gestational trophoblastic neoplasia (GTN). The parental type of most HMs are either diandric diploid (PP) or diandric triploid (PPM). We consecutively collected 154 triploid or near-triploid samples from conceptuses with vesicular chorionic villi. We used analysis of DNA markers and/or methylation sensitive-MLPA and collected data from registries and patients records. We performed whole genome SNP analysis of one case of twinning (PP+PM).In all 154 triploids or near-triploids we found two different paternal contributions to the genome (P1P2M). The ratios between the sex chromosomal constitutions XXX, XXY, and XYY were 5.7: 6.9: 1.0. No cases of GTN were observed. Our results corroborate that all triploid human conceptuses with vesicular chorionic villi have the parental type P1P2M. The sex chromosomal ratios suggest approximately equal frequencies of meiosis I and meiosis II errors with selection against the XYY conceptuses or a combination of dispermy, non-disjunction in meiosis I and meiosis II and selection against XYY conceptuses. Although single cases of GTN after a triploid HM have been reported, the results of this study combined with data from previous prospective studies estimate the risk of GTN after a triploid mole to 0% (95% CI: 0–1,4%).</p></div

Parental types in triploid conceptuses with molar phenotype.

<p>Parental types in triploid conceptuses with molar phenotype.</p

reproduced [7]. Possible fertilizations, endoreduplications, and abnormal cell divisions in mosaic hydatidiform moles (HMs), and twin gestations including an HM.

<p>(a) Fertilisation by two sperms; one giving rise to the paternal genome set in the diploid biparental cell population, the other giving rise to both genome sets in the diploid androgenetic cell population via endoreduplication. (b) Fertilisation by two sperms; one giving rise to one of the paternal genome sets in the diploid androgenetic cell population, the other contributing one genome set to both cell populations via endoreduplication. (c) Fertilisation by one sperm that via two endoreduplications gives rise to three identical paternal genome sets, of which two constitute the genome of the diploid androgenetic cell population and one is the paternal genome set in the diploid biparental cell population.</p

Number of fully informative loci in 152 (near) triploid cases with vesicular chorionic villi, analyzed along with a maternal sample.

<p>Number of fully informative loci in 152 (near) triploid cases with vesicular chorionic villi, analyzed along with a maternal sample.</p

SNP6 array analysis, C0301.

<p>SNP6 array analysis of individual C0301q and her twin pregnancy (C0301B (mole, PP) and C0301V (normal conceptus, PM)) demonstrating that the molar pregnancy was homozygous for all markers across the autosomal chromosomes and the X chromosome. Upper panel: Regions with stretches of markers showing homozygousity are displayed in purple. Lower panel: Genotypes (AA, AB, and BB) on chromosomes 1 for the three samples, illustrating the general absence of markers with genotype AB for the mole pregnancy. Each dot represents a genotyped SNP.</p

Minor allele frequency (MAF) and odds ratio (OR) of <i>MC1R</i> variants in melanoma cases/families compared to the Danish population.

<p>Minor allele frequency (MAF) and odds ratio (OR) of <i>MC1R</i> variants in melanoma cases/families compared to the Danish population.</p

Characteristics of the 13 individuals/families with identified <i>CDKN2A</i> mutations.

<p>SCC: squamous cell carcinoma</p><p>CLL: chronic lymphocytic leukemia</p><p>RCC: renal cell carcinoma</p><p>Characteristics of the 13 individuals/families with identified <i>CDKN2A</i> mutations.</p

Age at first melanoma in <i>CDKN2A</i> mutation carriers compared to age of first melanoma in individuals with melanoma and no <i>CDKN2A</i> mutation.

<p>Families with a <i>BAP1</i> mutation are not included, nor are individuals with UM.</p><p>Age at first melanoma in <i>CDKN2A</i> mutation carriers compared to age of first melanoma in individuals with melanoma and no <i>CDKN2A</i> mutation.</p

Minor allele frequency (MAF) and odds ratio (OR) of <i>MC1R</i> variants in melanoma cases/families compared to the Danish population.

<p>Minor allele frequency (MAF) and odds ratio (OR) of <i>MC1R</i> variants in melanoma cases/families compared to the Danish population.</p

<i>BAP1</i> analysed in individuals and families with CM and/or UM and mesothelioma.

<p><i>BAP1</i> analysed in individuals and families with CM and/or UM and mesothelioma.</p