Frequent homozygosity in both mature and immature ovarian teratomas: a shared genetic basis of tumorigenesis

• Published in: Modern pathology Vol. 30; no. 10; pp. 1467 - 1475
• Main Authors: Snir, Olivia L, DeJoseph, Maura, Wong, Serena, Buza, Natalia, Hui, Pei
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2017; Elsevier Limited
• Subjects: 13/51; 45; 45/77; 631/337/641; 692/699/67/68; Adolescent; Adult; Aged; Carcinogenesis - genetics; Deoxyribonucleic acid; DNA; Female; Genotyping; Germ cells; Humans; Laboratory Medicine; Medicine; Medicine & Public Health; Middle Aged; original-article; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Pathology; Teratoma; Teratoma - genetics; Teratoma - pathology; Tumorigenesis; Tumors; Young Adult; Zygosity
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.2017.66

Although homozygosity is well documented in mature teratomas, the genetic zygosity of ovarian immature teratomas and mixed germ cell tumors is less well studied. Ten cases of mature cystic teratomas, eleven cases of grade 2 or 3 immature teratomas, and seven cases of mixed germ cell tumors with an immature teratoma component were investigated by short tandem repeat genotyping to interrogate their genetic zygosity. DNA genotyping was informative in eight mature teratomas, seven immature teratomas and six cases of mixed germ cell tumors. Out of the eight mature teratomas, five cases showed partial or complete homozygosity (63%) with two cases demonstrating complete homozygosity (25%). Of the immature teratomas, six cases showed partial or complete homozygosity (86%) with two cases demonstrating complete homozygosity (29%). For the mixed germ cell tumors, two cases showed partial homozygosity (33%) and none displayed complete homozygosity. Long-term clinical follow-up was available for five immature teratomas (mean follow-up 110 months) and five mixed germ cell tumors (mean follow-up 66 months). None of the five patients with pure immature teratoma had a recurrence; in contrast, four out of five mixed ovarian germ cell tumors recurred between 4 months to 8 years ( P =0.048). In conclusion, both immature and mature teratomas harbor frequent genetic homozygosity suggesting a common cellular origin involving germ cells at the same developmental stage. The difference in the rate of homozygosity and tumor recurrence between pure immature teratomas and mixed germ cell tumors suggests that the two entities may involve different pathogenetic pathways and likely pursue different biological behaviors.