Tags

Type your tag names separated by a space and hit enter

Tubular, lactating, and ductal adenomas are devoid of MED12 Exon2 mutations, and ductal adenomas show recurrent mutations in GNAS and the PI3K-AKT pathway.
Genes Chromosomes Cancer. 2017 01; 56(1):11-17.GC

Abstract

Adenomas of the breast are rare benign tumors although single cases with malignant behavior have been reported. However, the genetic basis of these tumors is unknown. Employing targeted next generation sequencing of 50 cancer-related genes as well as Sanger sequencing, we profiled a cohort of 18 mammary adenomas comprising 9 ductal, 6 tubular, and 3 lactating adenoma. Missense mutations were detected in 8 of the 18 cases (44%). Specifically, five (56%) ductal adenomas and three (50%) tubular adenomas harbored mutated genes. No mutations were detected in lactating adenomas. Three of the nine ductal adenomas showed mutant AKT1 (p.E17K) with two of them harboring an additional GNAS mutation (p.R201C). One case had mutant PIK3CA (p.H1047R) and another case a mutation in GNAS (p.R201C). The three cases of mutated tubular adenomas showed mutations in either MET or FGFR3. Of note, we did not detect copy number changes and none of the cases including tubular adenomas had mutations in exon 2 of MED12. Our results suggest that ductal adenomas are related to papillomas of the breast and screening for mutations in exon 2 of MED12 might help to facilitate differential diagnosis between tubular adenoma and fibroadenoma in difficult cases. Lastly, our data exemplarily demonstrate that mutations in cancer-related genes per se do not indicate malignancy but occur in benign tumors. © 2016 Wiley Periodicals, Inc.

Authors+Show Affiliations

Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.Institute of Pathology, Technical University Munich (TUM), Munich, Germany.Institute of Pathology University Hospital Halle, Halle, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.Institute of Pathology, Charité University Hospital, Berlin, Germany.Institute of Pathology, Charité University Hospital, Berlin, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. Tissue Bank of the National Center for Tumor Diseases (NCT), Heidelberg, Germany.Institute of Pathology, Technical University Munich (TUM), Munich, Germany.Institute of Pathology, Technical University Munich (TUM), Munich, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany.Institute of Pathology University Hospital Halle, Halle, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany. National Center of Tumor Diseases, Heidelberg, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27438523

Citation

Volckmar, Anna-Lena, et al. "Tubular, Lactating, and Ductal Adenomas Are Devoid of MED12 Exon2 Mutations, and Ductal Adenomas Show Recurrent Mutations in GNAS and the PI3K-AKT Pathway." Genes, Chromosomes & Cancer, vol. 56, no. 1, 2017, pp. 11-17.
Volckmar AL, Leichsenring J, Flechtenmacher C, et al. Tubular, lactating, and ductal adenomas are devoid of MED12 Exon2 mutations, and ductal adenomas show recurrent mutations in GNAS and the PI3K-AKT pathway. Genes Chromosomes Cancer. 2017;56(1):11-17.
Volckmar, A. L., Leichsenring, J., Flechtenmacher, C., Pfarr, N., Siebolts, U., Kirchner, M., Budczies, J., Bockmayr, M., Ridinger, K., Lorenz, K., Herpel, E., Noske, A., Weichert, W., Klauschen, F., Schirmacher, P., Penzel, R., Endris, V., & Stenzinger, A. (2017). Tubular, lactating, and ductal adenomas are devoid of MED12 Exon2 mutations, and ductal adenomas show recurrent mutations in GNAS and the PI3K-AKT pathway. Genes, Chromosomes & Cancer, 56(1), 11-17. https://doi.org/10.1002/gcc.22396
Volckmar AL, et al. Tubular, Lactating, and Ductal Adenomas Are Devoid of MED12 Exon2 Mutations, and Ductal Adenomas Show Recurrent Mutations in GNAS and the PI3K-AKT Pathway. Genes Chromosomes Cancer. 2017;56(1):11-17. PubMed PMID: 27438523.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tubular, lactating, and ductal adenomas are devoid of MED12 Exon2 mutations, and ductal adenomas show recurrent mutations in GNAS and the PI3K-AKT pathway. AU - Volckmar,Anna-Lena, AU - Leichsenring,Jonas, AU - Flechtenmacher,Christa, AU - Pfarr,Nicole, AU - Siebolts,Udo, AU - Kirchner,Martina, AU - Budczies,Jan, AU - Bockmayr,Michael, AU - Ridinger,Kathrin, AU - Lorenz,Katja, AU - Herpel,Esther, AU - Noske,Aurelia, AU - Weichert,Wilko, AU - Klauschen,Frederick, AU - Schirmacher,Peter, AU - Penzel,Roland, AU - Endris,Volker, AU - Stenzinger,Albrecht, Y1 - 2016/08/09/ PY - 2016/03/23/received PY - 2016/07/13/revised PY - 2016/07/18/accepted PY - 2016/7/21/pubmed PY - 2017/7/22/medline PY - 2016/7/21/entrez SP - 11 EP - 17 JF - Genes, chromosomes & cancer JO - Genes Chromosomes Cancer VL - 56 IS - 1 N2 - Adenomas of the breast are rare benign tumors although single cases with malignant behavior have been reported. However, the genetic basis of these tumors is unknown. Employing targeted next generation sequencing of 50 cancer-related genes as well as Sanger sequencing, we profiled a cohort of 18 mammary adenomas comprising 9 ductal, 6 tubular, and 3 lactating adenoma. Missense mutations were detected in 8 of the 18 cases (44%). Specifically, five (56%) ductal adenomas and three (50%) tubular adenomas harbored mutated genes. No mutations were detected in lactating adenomas. Three of the nine ductal adenomas showed mutant AKT1 (p.E17K) with two of them harboring an additional GNAS mutation (p.R201C). One case had mutant PIK3CA (p.H1047R) and another case a mutation in GNAS (p.R201C). The three cases of mutated tubular adenomas showed mutations in either MET or FGFR3. Of note, we did not detect copy number changes and none of the cases including tubular adenomas had mutations in exon 2 of MED12. Our results suggest that ductal adenomas are related to papillomas of the breast and screening for mutations in exon 2 of MED12 might help to facilitate differential diagnosis between tubular adenoma and fibroadenoma in difficult cases. Lastly, our data exemplarily demonstrate that mutations in cancer-related genes per se do not indicate malignancy but occur in benign tumors. © 2016 Wiley Periodicals, Inc. SN - 1098-2264 UR - https://www.unboundmedicine.com/medline/citation/27438523/Tubular_lactating_and_ductal_adenomas_are_devoid_of_MED12_Exon2_mutations_and_ductal_adenomas_show_recurrent_mutations_in_GNAS_and_the_PI3K_AKT_pathway_ L2 - https://doi.org/10.1002/gcc.22396 DB - PRIME DP - Unbound Medicine ER -