Genetic alterations in cervical carcinomas: Frequent low‐level amplifications of oncogenes are associated with human papillomavirus infection

International Journal of Cancer - Tập 101 Số 5 - Trang 427-433 - 2002
Anju Zhang1, Susanne Månér1, Regina C. Betz2, T Ångström3, U Stendahl4, Frank Bergman3, Anders Zetterberg1, Keng‐Ling Wallin2
1Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
2Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden
3Laboratory of Clinical Cytology and Pathology, University Hospital, Umeå, Sweden
4Oncology Center, Umeå University, Umeå, Sweden

Tóm tắt

Abstract

The development of cervical carcinoma is closely associated with HPV infection. However, other genetic alterations also play an important role. In this study, we analyzed copy number alterations of several oncogene loci in a panel of 84 cervical tumors. Sixty‐five (77%) tumors were HPV DNA‐positive, and most were infected with type 16 or type 18 or both. The oncogenes studied include PIK3CA at 3q26.3, TERT at 5p15.33, C‐MYC at 8q24, CCND1 at 11q13.3, ERBB2 at 17q21.2 and locus region 20q13.2. Amplification of 1 or more genes was detected in 55 (65%) cases using interphase FISH. PIK3CA was amplified in 43% of tumors, followed by TERT (33%), 20q13.2 (30%), ERBB2 (29%), C‐MYC (25%) and CCND1 (12%). Most tumors showed low‐level amplification with 3–7 copies of these genes, and complex changes involving 3 or more genes occur more frequently in tumors at advanced stages. Increased protein expression of c‐erbB2 and c‐myc was observed in tumors with the corresponding gene amplification. Oncogene alterations were found more often in HPV‐infected cases, particularly for C‐MYC and TERT. These findings indicate that HPV‐associated cervical carcinomas bear frequent alterations of these genes, which may have critical biologic impact on the development and progression of carcinoma of the uterine cervix. © 2002 Wiley‐Liss, Inc.

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International Journal of Cancer

Tập 101 Số 5

427-433

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