Gestational trophoblastic disease: STR genotyping for precision diagnosis

Gestational trophoblastic disease (GTD) encompasses a constellation of rare to common gynecologic conditions stemming from aberrant gestations with distinct genetic backgrounds and variable degrees of trophoblast proliferation of either neoplastic or non-neoplastic nature. GTD is categorized into hydatidiform moles and gestational trophoblastic neoplasms, and their clinical outcomes vary widely across different subtypes. Prompt and accurate diagnosis plays a pivotal role in the effective management and prognostication of patients. Short tandem repeats (STRs) are repetitive DNA sequences dispersed throughout the human genome and inherit a tremendous genetic polymorphism among individuals. Widely recognized for its applications in forensic identity and paternity testing, the relevance of STR genotyping in the diagnosis of GTD has emerged as an essential ancillary test in the classification and management of GTD of both non-neoplastic hydatidiform moles and gestational trophoblastic tumors.

This review discusses fundamental principles, laboratory operation, and diagnostic interpretations of STR genotyping in the context of diagnosis and differential diagnosis of GTD. PubMed was searched for all references up to 2024.

STR genotyping is the gold standard in the diagnosis and subclassification of hydatidiform moles and has an important application in diagnostic workup and risk stratifications of gestational trophoblastic tumors as well.