Abstract
Abstract Purpose: Recent reports revealed that the kinase domain of the ERBB2 gene is somatically mutated in lung adenocarcinoma, suggesting the mutated ERBB2 gene as an oncogene in human cancers. However, because previous reports focused the mutational search of ERBB2 primarily on lung cancers, the data on ERBB2 mutations in other types of human cancers have been largely unknown. Experimental Design: Here, we did a mutational analysis of the ERBB2 kinase domain by PCR single-strand conformational polymorphism assay in gastric, colorectal, and breast carcinoma tissues. Results: We detected the ERBB2 kinase domain mutations in 9 of 180 gastric carcinomas (5.0%), in 3 of 104 colorectal carcinomas (2.9%), and in 4 of 94 breast carcinomas (4.3%). All of the detected ERBB2 mutations except for one in-frame deletion mutation were missense mutations. Of the 16 ERBB2 mutations detected, 4 affected Val777 in the exon 20 site, and 3 affected Leu755 in the exon 19 site. We simultaneously analyzed the somatic mutations of EGFR, K-RAS, PIK3CA, and BRAF genes in the 16 samples with ERBB2 mutations, and found that all of the 3 colorectal carcinoma samples with ERBB2 mutations harbored K-RAS mutations. Conclusion: This study showed that in addition to lung adenocarcinomas, ERBB2 kinase domain mutation occurs in other common human cancers such as gastric, breast, and colorectal cancers, and suggested that alterations of ERBB2-mediated signaling pathway by ERBB2 mutations alone or together with K-RAS mutations may contribute to the development of human cancers.
Bibliography
Lee, J. W., Soung, Y. H., Seo, S. H., Kim, S. Y., Park, C. H., Wang, Y. P., Park, K., Nam, S. W., Park, W. S., Kim, S. H., Lee, J. Y., Yoo, N. J., & Lee, S. H. (2006). Somatic Mutations of ERBB2 Kinase Domain in Gastric, Colorectal, and Breast Carcinomas. Clinical Cancer Research, 12(1), 57â61.
Authors
13
- Jong Woo Lee (first)
- Young Hwa Soung (additional)
- Si Hyung Seo (additional)
- Su Young Kim (additional)
- Cho Hyun Park (additional)
- Young Pil Wang (additional)
- Kyeongmee Park (additional)
- Suk Woo Nam (additional)
- Won Sang Park (additional)
- Sang Ho Kim (additional)
- Jung Young Lee (additional)
- Nam Jin Yoo (additional)
- Sug Hyung Lee (additional)
References
24
Referenced
181
-
Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer 2004;4:361–70.
(
10.1038/nrc1360
) -
Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 2003;284:31–53.
(
10.1016/S0014-4827(02)00098-8
) -
Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497–500.
(
10.1126/science.1099314
) -
Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–39.
(
10.1056/NEJMoa040938
) -
Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306–11.
(
10.1073/pnas.0405220101
) -
Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T, Mitsudomi T. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res 2004;64:8919–23.
(
10.1158/0008-5472.CAN-04-2818
) -
Holbro T, Civenni G, Hynes NE. The ErbB receptors and their role in cancer progression. Exp Cell Res 2003;284:99–110.
(
10.1016/S0014-4827(02)00099-X
) -
Citri A, Skaria KB, Yarden Y. The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp Cell Res 2003;284:54–65.
(
10.1016/S0014-4827(02)00101-5
) -
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987;235:177–82.
(
10.1126/science.3798106
) -
Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999;17:2639–48.
(
10.1200/JCO.1999.17.9.2639
) - Stephens P, Hunter C, Bignell G, et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 2004;431:525–6.
-
Shigematsu H, Takahashi T, Nomura M, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 2005;65:1642–6.
(
10.1158/0008-5472.CAN-04-4235
) -
Lee JY, Dong SM, Kim SY, Yoo NJ, Lee SH, Park WS. A simple, precise and economical microdissection technique for analysis of genomic DNA from archival tissue sections. Virchows Arch 1998;433:305–9.
(
10.1007/s004280050253
) -
Lee SH, Shin MS, Park WS, et al. Alterations of Fas (Apo-1/CD95) gene in non-small cell lung cancer. Oncogene 1999;18:3754–60.
(
10.1038/sj.onc.1202769
) - Lee SH, Shin MS, Kim HS, et al. Alterations of the DR5/TRAIL receptor 2 gene in non-small cell lung cancers. Cancer Res 1999;59:5683–6.
-
Lee JW, Soung YH, Kim SY, et al. Absence of EGFR mutation in the kinase domain in common human cancers besides non-small cell lung cancer. Int J Cancer 2005;113:510–1.
(
10.1002/ijc.20591
) -
Lee JW, Soung YH, Kim SY, et al. PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene 2005;24:1477–80.
(
10.1038/sj.onc.1208304
) -
Lee SH, Lee JW, Soung YH, et al. BRAF and KRAS mutations in stomach cancer. Oncogene 2003;22:6942–5.
(
10.1038/sj.onc.1206749
) -
Park K, Kwak K, Kim J, Lim S, Han S. c-myc amplification is associated with HER2 amplification and closely linked with cell proliferation in tissue microarray of nonselected breast cancers. Hum Pathol 2005;36:634–9.
(
10.1016/j.humpath.2005.04.016
) -
Slebos RJ, Hruban RH, Dalesio O, Mooi WJ, Offerhaus GJ, Rodenhuis S. Relationship between K-ras oncogene activation and smoking in adenocarcinoma of the human lung. J Natl Cancer Inst 1991;83:1024–7.
(
10.1093/jnci/83.14.1024
) -
Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554.
(
10.1126/science.1096502
) - Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949–54.
-
Klapper LN, Kirschbaum MH, Sela M, Yarden Y. Biochemical and clinical implications of the ErbB/HER signaling network of growth factor receptors. Adv Cancer Res 2000;77:25–79.
(
10.1016/S0065-230X(08)60784-8
) -
Futreal PA, Coin L, Marshall M, et al. A census of human cancer genes. Nat Rev Cancer 2004;4:177–83.
(
10.1038/nrc1299
)
Dates
Type | When |
---|---|
Created | 19 years, 5 months ago (March 21, 2006, 1:43 p.m.) |
Deposited | 3 years, 2 months ago (June 11, 2022, 2:53 p.m.) |
Indexed | 3 weeks, 4 days ago (Aug. 12, 2025, 5:41 p.m.) |
Issued | 19 years, 8 months ago (Jan. 1, 2006) |
Published | 19 years, 8 months ago (Jan. 1, 2006) |
Published Online | 19 years, 8 months ago (Jan. 5, 2006) |
Published Print | 19 years, 8 months ago (Jan. 1, 2006) |
@article{Lee_2006, title={Somatic Mutations of ERBB2 Kinase Domain in Gastric, Colorectal, and Breast Carcinomas}, volume={12}, ISSN={1557-3265}, url={http://dx.doi.org/10.1158/1078-0432.ccr-05-0976}, DOI={10.1158/1078-0432.ccr-05-0976}, number={1}, journal={Clinical Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Lee, Jong Woo and Soung, Young Hwa and Seo, Si Hyung and Kim, Su Young and Park, Cho Hyun and Wang, Young Pil and Park, Kyeongmee and Nam, Suk Woo and Park, Won Sang and Kim, Sang Ho and Lee, Jung Young and Yoo, Nam Jin and Lee, Sug Hyung}, year={2006}, month=jan, pages={57–61} }