Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer.
Standard
Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer. / Grob, Tobias; Heilenkötter, Uwe; Geist, Stefan; Paluchowski, Peter; Wilke, Christian; Jänicke, Fritz; Quaas, Alexander; Wilczak, Waldemar; Choschzick, Matthias; Sauter, Guido; Lebeau, Annette.
in: BREAST CANCER RES TR, Jahrgang 134, Nr. 2, 2, 2012, S. 561-567.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Rare oncogenic mutations of predictive markers for targeted therapy in triple-negative breast cancer.
AU - Grob, Tobias
AU - Heilenkötter, Uwe
AU - Geist, Stefan
AU - Paluchowski, Peter
AU - Wilke, Christian
AU - Jänicke, Fritz
AU - Quaas, Alexander
AU - Wilczak, Waldemar
AU - Choschzick, Matthias
AU - Sauter, Guido
AU - Lebeau, Annette
PY - 2012
Y1 - 2012
N2 - Women with triple-negative breast cancer (TNBC) do not benefit from endocrine therapy or trastuzumab. Chemotherapy is the only systemic therapy currently available. To reduce the elevated risk of disease progression in these patients, better treatment options are needed, which are less toxic and more targeted to this patient population. We performed a comprehensive analysis of potential targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK pathway, which are observed at higher frequencies in adenocarcinomas of other organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2 (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple-negative status was confirmed by immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6 immunohistochemical analyses were performed for identification of the basal-like phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included. Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS, and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein expression was observed in only one case. No rearrangement of the ALK gene was detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %). TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway occur rarely in TNBC.
AB - Women with triple-negative breast cancer (TNBC) do not benefit from endocrine therapy or trastuzumab. Chemotherapy is the only systemic therapy currently available. To reduce the elevated risk of disease progression in these patients, better treatment options are needed, which are less toxic and more targeted to this patient population. We performed a comprehensive analysis of potential targetable genetic aberrations affecting the receptor tyrosine kinase/RAS/MAPK pathway, which are observed at higher frequencies in adenocarcinomas of other organs. Sixty-five individual TNBCs were studied by sequence analysis for HER2 (exon 18-23), EGFR (exon 18-21), KRAS (exon 2), and BRAF (exon 15) mutations. In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple-negative status was confirmed by immunohistochemistry and FISH on tissue microarray sections. EGFR and CK5/6 immunohistochemical analyses were performed for identification of the basal-like phenotype. In addition, mutation analysis of TP53 (exon 5-8) was included. Sequence analysis revealed HER2 gene mutation in only one patient (heterozygous missense mutation in exon 19: p.L755S). No mutations were found in EGFR, KRAS, and BRAF. High polysomy of EGFR was detected in 5 of the 62 informative cases by FISH. True EGFR gene amplification accompanied by strong membranous EGFR protein expression was observed in only one case. No rearrangement of the ALK gene was detected. Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5 %). TP53 gene mutation was found in 36/63 (57.1 %) tumors. We conclude that targetable genetic aberrations in the receptor tyrosine kinase/RAS/MAPK pathway occur rarely in TNBC.
KW - Adult
KW - Humans
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - DNA Mutational Analysis
KW - Base Sequence
KW - Gene Dosage
KW - Gene Amplification
KW - In Situ Hybridization, Fluorescence
KW - Tissue Array Analysis
KW - Receptor, Epidermal Growth Factor/genetics
KW - Tumor Suppressor Protein p53/genetics
KW - Receptors, Progesterone/metabolism
KW - Oncogenes
KW - Mutation
KW - Receptor Protein-Tyrosine Kinases/genetics
KW - Receptors, Estrogen/metabolism
KW - Proto-Oncogene Proteins B-raf/genetics
KW - Proto-Oncogene Proteins/genetics
KW - Breast Neoplasms/drug therapy/genetics/metabolism
KW - Carcinoma, Ductal, Breast/drug therapy/genetics/metabolism
KW - Receptor, erbB-2/genetics/metabolism
KW - ras Proteins/genetics
KW - Adult
KW - Humans
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - DNA Mutational Analysis
KW - Base Sequence
KW - Gene Dosage
KW - Gene Amplification
KW - In Situ Hybridization, Fluorescence
KW - Tissue Array Analysis
KW - Receptor, Epidermal Growth Factor/genetics
KW - Tumor Suppressor Protein p53/genetics
KW - Receptors, Progesterone/metabolism
KW - Oncogenes
KW - Mutation
KW - Receptor Protein-Tyrosine Kinases/genetics
KW - Receptors, Estrogen/metabolism
KW - Proto-Oncogene Proteins B-raf/genetics
KW - Proto-Oncogene Proteins/genetics
KW - Breast Neoplasms/drug therapy/genetics/metabolism
KW - Carcinoma, Ductal, Breast/drug therapy/genetics/metabolism
KW - Receptor, erbB-2/genetics/metabolism
KW - ras Proteins/genetics
M3 - SCORING: Journal article
VL - 134
SP - 561
EP - 567
JO - BREAST CANCER RES TR
JF - BREAST CANCER RES TR
SN - 0167-6806
IS - 2
M1 - 2
ER -