Distinct genomic profiles of gestational choriocarcinoma, a unique cancer of pregnant tissues

• Published in: Experimental & molecular medicine 2020, 52(0), , pp.1-9
• Main Authors: Jung, Seung-Hyun, Choi, Youn Jin, Kim, Min Sung, Park, Hyeon-Chun, Han, Mi-Ryung, Hur, Soo Young, Lee, Ah Won, Shin, Ok Ran, Kim, Jeana, Lee, Sung Hak, Hong, Dongwan, Song, Sang Yong, Chung, Yeun-Jun, Lee, Sug Hyung
• Format: Article
• Language: English
• Subjects: 38; 45/22; 45/23; 45/47; 45/77; 631/67/69; 692/699/67/1517/1931; Alleles; Biomedical and Life Sciences; Biomedicine; Cancer; Choriocarcinoma - diagnosis; Choriocarcinoma - genetics; Choriocarcinoma - mortality; Chromatin remodeling; Chromosomes; Copy number; Disease Susceptibility; DNA Copy Number Variations; DNA microarrays; Female; Gene mapping; Genetic Variation; Genomic analysis; Genomics; Heterozygosity; Humans; Hydatidiform mole; Invasiveness; Loss of Heterozygosity; Malignancy; Medical Biochemistry; Metastases; Microsatellite Repeats; Molecular Medicine; Mutation; p53 Protein; Placenta; Polymorphism, Single Nucleotide; Pregnancy; Prognosis; Single-nucleotide polymorphism; Solid tumors; Stem Cells; Tumors; Uterine Neoplasms - diagnosis; Uterine Neoplasms - genetics; Uterine Neoplasms - mortality; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-020-00544-0

Little is known about genomic alterations of gestational choriocarcinoma (GC), unique cancer that originates in pregnant tissues, and the progression mechanisms from the nonmalignant complete hydatidiform mole (CHM) to GC. Whole-exome sequencing (20 GCs) and/or single-nucleotide polymorphism microarray (29 GCs) were performed. We analyzed copy-neutral loss-of-heterozygosity (CN-LOH) in 29 GCs that exhibited androgenetic CN-LOHs (20 monospermic, 8 dispermic) and no CN-LOH (one with NLRP7 mutation). Most GCs (25/29) harboring recurrent copy number alterations (CNAs) and gains on 1q21.1-q44 were significantly associated with poor prognosis. We detected five driver mutations in the GCs, most of which were chromatin remodeling gene ( ARID1A , SMARCD1 , and EP300 ) mutations but not in common cancer genes such as TP53 and KRAS . One patient’s serial CHM/invasive mole/GC showed consistent CN-LOHs, but only the GC harbored CNAs, indicating that CN-LOH is an early pivotal event in HM-IM-GC development, and CNAs may be a late event that promotes CHM progression to GC. Our data indicate that GCs have unique profiles of CN-LOHs, mutations and CNAs that together differentiate GCs from non-GCs. Practically, CN-LOH and CNA profiles are useful for the molecular diagnosis of GC and the selection of GC patients with poor prognosis for more intensive treatments, respectively. Cancer: Mapping markers of maternal malignancy Genomic analysis reveals chromosomal alterations that drive disease progression in a poorly understood class of tumors that form in placental tissue. Gestational choriocarcinoma (GC) arises during pregnancy and can quickly develop into lethal metastatic disease if not treated promptly. To identify the origins of such malignancies, researchers led by Sug Hyung Lee and Yeun-Jun Chung at The Catholic University of Korea, Seoul, profiled genetic aberrations in 29 GC specimens. The researchers did not observe any consistent link between these malignancies and a particular set of ‘driver mutations’ underlying tumor progression as has been seen in other solid tumors. However, these GC samples exhibited striking levels of rearrangement between chromosomes. The researchers propose that the gain or loss of genes resulting from these chromosomal abnormalities may be an important contributor to rapidly progressing forms of this disease.