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The coexistence of ERBB2, INT2, and CMYC oncogene amplifications and PTEN gene mutations in endometrial carcinoma

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Abstract

Purpose

To evaluate the frequency of ERBB2, INT2 and CMYC oncogene amplifications and their coexistence with PTEN gene mutations in endometrial carcinomas.

Methods

In 54 endometrial carcinomas amplification of ERBB2, INT2 and CMYC was determined using differential polymerase chain reaction (dPCR), and mutations in all exons of PTEN were investigated by PCR-SSCP and direct sequencing methods. Results were correlated with clinicopathological features of tumors.

Results

In 31 out of 54 endometrial carcinomas (57.4%) genetic defects were found within the examined genes. Of all identified defects, mutations in PTEN and the amplification of CMYC were most frequent (26/54–48.1% and 10/54–18.5%, respectively). INT2 was amplified in 5.6% (3/54) of cases. In no case did we find ERBB2 amplification. In 77.4% (24/31) of cases only one gene was damaged. Of these, 20 cases showed only PTEN mutations, three cases only CMYC, and one case only INT2 amplification. In another seven out of 31 tumors (22.5%) defects in two or three genes coexisted simultaneously: PTEN and CMYC in five cases, CMYC and INT2 in one case, and PTEN, CMYC, and INT2 in one case. We found a number of interesting relations between the location of mutations within the PTEN sequence and the presence (+) or lack (-) of CMYC amplification. In the PTEN+CMYC- tumors the PTEN mutations were most frequent in exons 1–5, and less frequent in exons 7–8 (66.7% and 33.3%, respectively). In contrast, in the PTEN+CMYC+ carcinomas the PTEN mutations were found mainly in exons 7–8 (85.7%). PTEN mutations were equally frequent in both early and more advanced endometrial carcinomas. The CMYC amplification, however, was more frequent in advanced as compared to early tumors, although this difference did not reach statistical significance.

Conclusions

Our data suggest that differences in the presence of genetic defects may reflect the different molecular pathways of endometrial carcinogenesis. These data also suggest that location of intragenic PTEN mutations and their coexistence with the CMYC amplification may play a crucial part in the development of various subtypes of endometrial carcinoma, but this preliminary suggestion requires further research.

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Authors and Affiliations

  1. Endocrinology Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 5 W.K. Roentgen Street, 02-781, Warsaw, Poland

    Bożena Konopka, Aneta Janiec-Jankowska & Zygmunt Paszko

  2. 2nd Department of Gynecology, Medical Academy, Wroclaw, Poland

    Marian Goluda

Authors
  1. Bożena Konopka
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  2. Aneta Janiec-Jankowska
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  3. Zygmunt Paszko
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  4. Marian Goluda
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Correspondence to Bożena Konopka.

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Konopka, B., Janiec-Jankowska, A., Paszko, Z. et al. The coexistence of ERBB2, INT2, and CMYC oncogene amplifications and PTEN gene mutations in endometrial carcinoma. J Cancer Res Clin Oncol 130, 114–121 (2004). https://doi.org/10.1007/s00432-003-0518-7

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  • DOI: https://doi.org/10.1007/s00432-003-0518-7

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