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TP53 and metaplastic breast cancer

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https://www.readbyqxmd.com/read/27531819/comprehensive-profiling-of-metaplastic-breast-carcinomas-reveals-frequent-overexpression-of-programmed-death-ligand-1
#1
Upasana Joneja, Semir Vranic, Jeffrey Swensen, Rebecca Feldman, Wangjuh Chen, Jeffrey Kimbrough, Nianqing Xiao, Sandeep Reddy, Juan Palazzo, Zoran Gatalica
AIMS: Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy than ductal carcinoma. In molecular terms, MBCs usually cluster with triple-negative breast cancers (TNBCs), but have a worse prognosis than TNBCs. Studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches. The aim of the present study was to characterise MBCs on a molecular level and test programmed death-ligand 1 (PD-L1) biomarker expression in MBCs for future therapeutic interventions...
August 16, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27220763/prognostic-factors-in-the-myoepithelial-like-spindle-cell-type-of-metaplastic-breast-cancer
#2
Fabian Leo, Stephan Bartels, Lavinia Mägel, Theodor Framke, Guntram Büsche, Danny Jonigk, Matthias Christgen, Ulrich Lehmann, Hans Kreipe
Metaplastic breast carcinoma (MBC) comprises a heterogeneous group of tumors with difficult to predict biological behavior. A subset of MBC, characterized by spindle-shaped tumor cells with a myoepithelial-like immunophenotype, was entered into a retrospective study (n = 42, median follow-up time 43 months). Molecular parameters (DNA sequences of mutation hot spots in AKT1, ALK, APC, BRAF, CDH1, CTNNB1, EGFR, ERBB2, FBXW7, FGFR2, FOXL2, GNAQ, GNAS, KIT, KRAS, MAP2K1, MET, MSH6, NRAS, PDGFRA, PIK3CA, PTEN, SF3B1, SMAD4, SRC, SRSF2, STK11, TP53, and U2AF1; copy numbers for EGFR, c-myc, FGFR, PLAG, c-met) were assessed...
August 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/26907767/whole-exome-sequencing-of-rare-aggressive-breast-cancer-histologies
#3
Maria Vittoria Dieci, Veronika Smutná, Véronique Scott, Guangliang Yin, Ran Xu, Philippe Vielh, Marie-Christine Mathieu, Cécile Vicier, Melanie Laporte, Francoise Drusch, Valentina Guarneri, Pierfranco Conte, Suzette Delaloge, Ludovic Lacroix, Olivia Fromigué, Fabrice André, Celine Lefebvre
Little is known about mutational landscape of rare breast cancer (BC) subtypes. The aim of the study was to apply next generation sequencing to three different subtypes of rare BCs in order to identify new genes related to cancer progression. We performed whole exome and targeted sequencing of 29 micropapillary, 23 metaplastic, and 27 pleomorphic lobular BCs. Micropapillary BCs exhibit a profile comparable to common BCs: PIK3CA, TP53, GATA3, and MAP2K4 were the most frequently mutated genes. Metaplastic BCs presented a high frequency of TP53 (78 %) and PIK3CA (48 %) mutations and were recurrently mutated on KDM6A (13 %), a gene involved in histone demethylation...
February 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/25927147/genomic-profiling-of-advanced-stage-metaplastic-breast-carcinoma-by-next-generation-sequencing-reveals-frequent-targetable-genomic-abnormalities-and-potential-new-treatment-options
#4
Jeffrey S Ross, Sunil Badve, Kai Wang, Christine E Sheehan, Ann B Boguniewicz, Geoff A Otto, Roman Yelensky, Doron Lipson, Siraj Ali, Deborah Morosini, Juliann Chliemlecki, Julia A Elvin, Vincent A Miller, Philip J Stephens
CONTEXT: Metastatic metaplastic breast carcinoma (MPBC) is an uncommon, but aggressive, tumor resistant to conventional chemotherapy. OBJECTIVE: To learn whether next-generation sequencing could identify potential targets of therapy for patients with relapsed and metastatic MPBC. DESIGN: Hybridization capture of 3769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to a minimum of 50 ng of DNA extracted from 20 MPBC formalin-fixed, paraffin-embedded specimens and sequenced to high uniform coverage...
May 2015: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/25320628/combined-antiangiogenic-and-mammalian-target-of-rapamycin-inhibitor-targeted-therapy-in-metaplastic-breast-cancer-harboring-a-pik3ca-mutation
#5
Rishi Agarwal, Kimberly Koenig, Eric Rohren, Vivek Subbiah
Metaplastic breast cancer (MpBC) is an extremely rare breast cancer subtype, characterized by a heterogeneous phenotype. MpBC aggressive biology is attributed to its stem cell-like characteristics. Since these tumors are largely chemoresistant, novel targeted therapies should be explored. Herein, we report the clinical course of a 59-year-old African American woman with MpBC with a PIK3CA mutation in codon 545, exon 10 (GAG to AAG; p.Glu545Lys) and a TP53 mutation in codon 286, exon 8 (GAA to AAA; p.Glu286Lys)...
September 2014: Journal of Breast Cancer
https://www.readbyqxmd.com/read/23873024/prolactin-cooperates-with-loss-of-p53-to-promote-claudin-low-mammary-carcinomas
#6
K A O'Leary, D E Rugowski, R Sullivan, L A Schuler
TP53 is one of the most commonly mutated genes in cancer. In breast cancer, it is mutated in about 40% of primary clinical tumors and is associated with poor survival. The mammotrophic hormone, prolactin (PRL), and/or its receptor are also expressed in many breast cancers, and accumulating epidemiologic data link PRL to breast cancer development and progression. Like TP53 mutations, evidence for PRL activity is evident across several molecular cancer subtypes, and elevated PRL expression and loss of p53 have been observed in some of the same clinical tumors...
June 5, 2014: Oncogene
https://www.readbyqxmd.com/read/23374397/first-description-of-an-acinic-cell-carcinoma-of-the-breast-in-a-brca1-mutation-carrier-a-case-report
#7
Carla B Ripamonti, Mara Colombo, Patrizia Mondini, Manoukian Siranoush, Bernard Peissel, Loris Bernard, Paolo Radice, Maria Luisa Carcangiu
BACKGROUND: Acinic cell carcinoma (ACC) is a rare malignant epithelial neoplasm characterized by the presence of malignant tubular acinar exocrine gland structures. Diagnosis is generally made in salivary glands and in the pancreas. ACC of the breast has been reported in few cases only. Carriers of inherited mutations in the BRCA1 gene are prone to the development of breast cancer, mainly invasive ductal or medullary type carcinomas. We describe for the first time a BRCA1 mutation carrier with a diagnosis of ACC of the breast...
2013: BMC Cancer
https://www.readbyqxmd.com/read/20099298/molecular-analysis-reveals-a-genetic-basis-for-the-phenotypic-diversity-of-metaplastic-breast-carcinomas
#8
Felipe C Geyer, Britta Weigelt, Rachael Natrajan, Maryou B K Lambros, Dario de Biase, Radost Vatcheva, Kay Savage, Alan Mackay, Alan Ashworth, Jorge S Reis-Filho
Cancers may be composed of multiple populations of submodal clones sharing the same initiating genetic lesions, followed by the acquisition of divergent genetic hits. Intra-tumour genetic heterogeneity has profound implications for cancer clinical management. To determine the extent of intra-tumour genetic heterogeneity in breast cancers, and whether the morphological diversity of breast cancers is underpinned by divergent genetic aberrations, we analysed the genomic profiles of microdissected, morphologically distinct components of six metaplastic breast carcinomas, tumours characterized by the presence of morphological areas with divergent differentiation...
April 2010: Journal of Pathology
https://www.readbyqxmd.com/read/19657711/clinicopathological-characteristics-of-triple-negative-breast-cancers
#9
Yuka Sasaki, Hitoshi Tsuda
Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors and HER2. Although patients with TNBC tend to have a poor prognosis, only chemotherapy is expected to be effective because no therapeutic targets have yet been established. DNA microarray analyses have proved that TNBCs are composed of the basal-like subtype and normal breast (or unclassified) subtype, the former being correlated with an aggressive clinical course. Histological types of TNBCs are reported to be common with those of basal-like subtype, comprising high-grade invasive ductal carcinoma, no special type [solid-tubular carcinoma (or atypical medullary carcinoma), invasive ductal carcinoma with a large central acellular zone], typical medullary carcinoma, and metaplastic carcinomas...
2009: Breast Cancer: the Journal of the Japanese Breast Cancer Society
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