Molecular landscape of copy number alterations and genetic mutations in high-grade serous adenocarcinoma of the ovary

DOI Web Site
  • Fukagawa Tomoyuki
    Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Japan Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka, Japan
  • Sugai Tamotsu
    Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Japan
  • Habano Wataru
    Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University, Yahaba, Japan
  • Eizuka Makoto
    Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Japan
  • Uesugi Noriyuki
    Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Japan
  • Osakabe Mitsumasa
    Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Japan
  • Suga Yasuko
    Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka, Japan
  • Nagasawa Takayuki
    Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka, Japan
  • Itamochi Hiroaki
    Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka, Japan
  • Sugiyama Toru
    Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka, Japan

Bibliographic Information

Other Title
  • 卵巣高異型度漿液性腺癌における高密度SNP arrayを用いた分子解析

Search this article

Abstract

Ovarian cancer (OC) is the leading cause of cancer-related death for gynecological cancers. In particular, high-grade serous adenocarcinoma (HGSA) is the most common and aggressive type of OC. Although HGSA exhibits complex genetic alterations, including copy number alterations (CNAs), the molecular mechanisms of HGSA pathogenesis are not fully understood. Single-nucleotide polymorphisms were used to examine genome-wide alterations in ovarian HGSAs. In addition, mutations in TP53, KRAS, BRAF, and PIK3CA were examined. The highest frequencies of gains in HGSA were found at 8q21-24.3, 3q25.2-27.2, 1q43, and 20q13.33. The most frequent LOHs in HGSA were at 5q12.1-13.3, 4q22.2 -24, 8p21.3-22, 16q22.2-23.1, and 22q13.31. In addition, regions of copy-neutral (CN)-LOHs (CN-LOH) in HGSA were detected at 17q21-25 and 17q11-13. The total lengths of the CN-LOHs were significantly greater in HGSA with lymph node metastasis than in that without lymph node metastasis. Although mutations in TP53 were frequent, mutations in KRAS, BRAF, and PIK3CA were rarely found in the HGSA specimens examined. The total lengths of the gains were significantly greater in HGSA with TP53 mutation than in that without TP53 mutation. Additionally, concurrent TP53 mutation and CN-LOH at 17p13.1 were frequently found in HGSA. Significant differences in gains between lymph node-positive and -negative samples were observed at 6q16.2-16.3, 6q22.31, and 16q13.2. Furthermore, there were significant differences in the regions of CN-LOH at 9p21-23. These findings suggest the usefulness of genome-wide alterations for the detection of novel frequent genetic alterations that may contribute to HGSA onset or progression.

Journal

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top