Amplification and Overexpression of the L-MYC Proto-Oncogene in Ovarian Carcinomas

Wu, Rong; Lin, Lin; Beer, David G.; Ellenson, Lora Hedrick; Lamb, Barbara; Rouillard, Jean Marie; Kuick, Rork; Hanash, Samir M.; Schwartz, Donald R.; Fearon, Eric R.; Cho, Kathleen R.

doi:10.1016/s0002-9440(10)64294-0

Cited by 59 publications

(41 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A genome-wide search for DNA copy number gains in HNSCC RLGS allows the detection of low-level DNA copy number changes and has been used in the past to identify several proto-oncogenes, including the cyclindependent kinase, CDK6, in glioblastomas (Costello et al, 1997), MYCL in ovarian carcinomas (Wu et al, 2003), and inhibitors of apoptosis, cIAP1 and cIAP2, in lung carcinomas (Dai et al, 2003). Here we used RLGS analysis on paired primary tumor and normal adjacent tissues from HNSCC patient samples for the identification of copy number gains.…”

Section: Resultsmentioning

confidence: 99%

DNA copy number gains in head and neck squamous cell carcinoma

et al. 2005

View full text Add to dashboard Cite

Gene amplification, a common mechanism for oncogene activation in cancer, has been used as a tag for the identification of novel oncogenes. DNA amplification is frequently observed in head and neck squamous cell carcinoma (HNSCC) and potential oncogenes have already been reported. We applied restriction landmark genome scanning (RLGS) to study gene amplifications and low-level copy number changes in HNSCC in order to locate previously uncharacterized regions with copy number gains in primary tumor samples. A total of 63 enhanced RLGS fragments, indicative of DNA copy number changes, including gains of single alleles, were scored. Enhanced sequences were identified from 33 different chromosomal regions including those previously reported (e.g. 3q26.3 and 11q13.3) as well as novel regions (e.g. 3q29, 8q13.1, 8q22.3, 9q32, 10q24.32, 14q32.32, 17q25.1 and 20q13.33). Furthermore, our data suggest that amplicons 11q13.3 and 3q26.3-q29 may be divided into possibly two and three independent amplicons, respectively, an observation supported by published microarray expression data.

show abstract

Section: Resultsmentioning

confidence: 99%

DNA copy number gains in head and neck squamous cell carcinoma

et al. 2005

View full text Add to dashboard Cite

show abstract

“…In comparison, some other genes showed higher rates of amplifications in these cancers. For example, the amplification of ERBB2 ranges (0-66%), 25,26 EGFR (3.65-12%), 27,28 CCND1 (0-19%), [29][30][31] C-MYC up to 54.5, 25,32,33 and KRAS (31%). 33 The significant frequency of estrogen receptor positivity in ovarian cancers had prompted treatment efforts using hormonal therapy early on.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor gene amplification occurs rarely in ovarian cancer

et al. 2009

View full text Add to dashboard Cite

Amplification of the gene encoding estrogen receptor-a occurs in about 20% of breast cancers and is an important mechanism for estrogen receptor overexpression in this tumor type. In ovarian cancer, overexpression of estrogen receptor protein has been described in more than two thirds of cases. To study a potential role of estrogen receptor-a gene amplification for estrogen receptor overexpression in ovarian cancer, a tumor tissue microarray containing 428 ovarian cancers was analyzed by fluorescence in situ hybridization for estrogen receptor-a gene amplification and immunohistochemistry for estrogen receptor expression. The estrogen receptor-a gene status was successfully determined in 243 of 428 arrayed cancers. Estrogen receptor gene amplification was found in 5 of 243 (2%) of tumors. Amplification levels were usually low, with 4-8 estrogen receptor-a gene copies. However, one case had a high-level amplification, with more than 30 estrogen receptor-a gene copies. Keywords: ovarian cancers; estrogen receptor-a gene; estrogen receptors; fluorescence in situ hybridization; immunohistochemistry Worldwide, ovarian cancer is the fifth most frequent malignant tumor in women and the most common cause of death among cancers of the reproductive system.1 Prognosis is generally poor as these cancers are often detected in late stage. The median overall survival in these patients is 24-38 months after diagnosis. 2Treatment options include surgical removal of the tumor mass with a maximal reduction of the peritoneal cancer mass in case of local tumor extension. In addition, topical and systemic cytotoxic therapy is applied. Ovarian cancer belongs to the group of cancers with frequent expression of steroid hormone receptors. Depending on the study estrogen receptor expression has been reported in 25-86% of ovarian cancers with the highest percentages reported in endometroid and serous subtypes.3-16 Accordingly, endocrine therapy is a recognized option in the treatment of chemoresistant ovarian cancer after the failure of first-and second-line therapies. However, not all estrogen receptor-positive ovarian cancers respond to antiestrogen therapy, and it was suggested that it might be because of the facts that most of the studies have been retrospective, small in size without adequate selection of the patients and generally used hormonal therapy as a last-line therapy for the refractory or resistant ovarian cancers. Moreover, concerning tamoxifen, it has not been definitely clarified whether it only acts as a pure estrogen antagonist in ovarian tissue, or it has also an agonist effects. 17-21In breast cancer, we had recently described estrogen receptor-a (ESR1) gene amplification as a frequent mechanism for estrogen receptor overexpression. More than 20% of breast cancers showed ESR1 gene amplification and more than 15% additional cases low-level ESR1 gene copy number gains.22 Preliminary data also suggested that ESR1 amplified breast cancers may exhibit a high responsiveness to tamoxifen. To determine, whether ESR1 amplificat...

show abstract

“…Despite considerable efforts aimed at elucidating the molecular etiology of ovarian serous carcinoma, its pathogenesis is still largely unknown. Although many genes have been previously reported to be amplified and deleted in ovarian cancer, [6][7][8][9][10][11][12][13] the overall profile of DNA copy number alterations in high-grade serous carcinomas has not been well described. One of the reasons is that most previous studies have combined different histological types of ovarian cancer, and therefore the specific alterations in the different histological types of ovarian serous carcinoma are not known.…”

mentioning

confidence: 99%

Amplicon profiles in ovarian serous carcinomas

Nakayama

Jinawath

et al. 2007

Intl Journal of Cancer

122

113

View full text Add to dashboard Cite

Ovarian serous carcinoma is the most common and lethal type of ovarian cancer and its molecular etiology remains poorly understood. As an ongoing effort to elucidate the pathogenesis of ovarian serous carcinomas, we assessed the DNA copy number changes in 33 high-grade serous carcinomas and 10 low-grade serous tumors by using a genome-wide technique, single nucleotide polymorphism array, performed on affinity-purified tumor cells from fresh surgical specimens. Compared to low-grade tumors, highgrade serous carcinomas showed widespread DNA copy number changes. The most frequent alterations were in loci harboring candidate oncogenes: cyclin E1 (CCNE1), AKT2, Notch3 and PIK3CA as well as in novel loci, including 12p13, 8q24, 12p13 and 12q15. Seven amplicons were selected for dual color fluorescence in situ hybridization analysis in 90 high-grade serous carcinomas and 26 low-grade serous tumors, and a high level of DNA copy number gain (amplification) was found in CCNE1, Notch3, HBXAP/Rsf-1, AKT2, PIK3CA and chr12p13 occurring in 36.1%, 7.8%, 15.7%, 13.6%, 10.8% and 7.3% of high-grade serous carcinomas. In contrast, we did not observe high level of ERBB2 amplification in any of the samples. Low-grade tumors did not show DNA copy number gain in any of the loci, except in 2 (8%) of 24 low-grade tumors showing low copy number gain in the Notch3 locus. Taken together, our results provide the first comprehensive analysis of DNA copy number changes in highly pure ovarian serous carcinoma. These findings may have important biological and clinical implications. ' 2007 Wiley-Liss, Inc.

show abstract

Amplification and Overexpression of the L-MYC Proto-Oncogene in Ovarian Carcinomas

Cited by 59 publications

References 48 publications

DNA copy number gains in head and neck squamous cell carcinoma

DNA copy number gains in head and neck squamous cell carcinoma

Estrogen receptor gene amplification occurs rarely in ovarian cancer

Amplicon profiles in ovarian serous carcinomas

Contact Info

Product

Resources

About