Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers

Santarpia, Libero; Qi, Yuan; Stemke-Hale, Katherine; Wang, Bailiang; Young, Elliana; Booser, Daniel J.; Holmes, Frankie A.; O’Shaughnessy, Joyce; Hellerstedt, Beth A.; Pippen, John; Vidaurre, Tatiana; Gómez, Henry L.; Valero, Vicente; Hortobágyi, Gabriel N.; Symmans, W. Fraser; Bottai, Giulia; Leo, Angelo Di; González-Angulo, Ana M.; Pusztai, Lajos

doi:10.1007/s10549-012-2035-3

Cited by 105 publications

(71 citation statements)

References 19 publications

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“…Studies that included small numbers of MC demonstrated that mutated PIK3CA, which is found in 16-33% of IDCs, is not a common finding in MC (0-13%), supplementary material, Figure S8 [125,[152][153][154][155][156][157]. Mutations of BRAF and KRAS are not common in breast cancer (0-3% and 2-5%) and associations with MC have not been studied [65,158,159]. Unlike in colorectal MC, MSI is a rare phenomenon in MC of the breast, occurring only sporadically (0-3%) [160][161][162][163][164][165].…”

Section: Mucinous Breast Carcinomamentioning

confidence: 99%

The molecular background of mucinous carcinoma beyond MUC2

Hugen

Simons²,

Halilović³

et al. 2014

Clin J Pathol

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The increasing interest of the oncology community in tumour classification and prediction of outcome to targeted therapies has put emphasis on an improved identification of tumour types. Colorectal mucinous adenocarcinoma (MC) is a subtype that is characterized by the presence of abundant extracellular mucin that comprises at least 50% of the tumour volume and is found in 10-15% of colorectal cancer patients. MC development is poorly understood, however, the distinct clinical and pathological presentation of MC suggests a deviant development and molecular background. In this review we identify common molecular and genetic alterations in colorectal MC. MC is characterized by a high rate of MUC2 expression. Mutation rates in the therapeutically important RAS/RAF/MAPK and PI3K/AKT pathways are significantly higher in MC compared with non-mucinous adenocarcinoma. Furthermore, mucinous adenocarcinoma shows higher rates of microsatellite instability and is more frequently of the CpG island methylator phenotype. Although the majority of MCs arise from the large intestine, this subtype also develops in other organs, such as the stomach, pancreas, biliary tract, ovary, breast and lung. We compared findings from colorectal MC with tumour characteristics of MCs from other organs. In these organs, MCs show different mutation rates in the RAS/RAF/MAPK and PI3K/ AKT pathways as well, but a common mucinous pathway cannot be identified. Identification of conditions and molecular aberrations that are associated with MC generates insight into the aetiology of this subtype and improves understanding of resistance to therapies.

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Section: Mucinous Breast Carcinomamentioning

confidence: 99%

The molecular background of mucinous carcinoma beyond MUC2

Hugen

Simons²,

Halilović³

et al. 2014

Clin J Pathol

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“…Patients with TNBC show a significant worse prognosis compared with other breast cancer subtypes (1). However, increasing evidence indicates that TNBC is a heterogeneous disease that encompasses several distinct entities with remarkably different molecular characteristics and clinical behavior (1)(2)(3). No specific and well-defined molecular targets have so far been found in TNBC and there seem to be few therapeutic options on the horizon.…”

Section: Introductionmentioning

confidence: 99%

A Serum MicroRNA Signature Predicts Tumor Relapse and Survival in Triple-Negative Breast Cancer Patients

Sahlberg

Bottai

Naume

et al. 2015

Clinical Cancer Research

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189

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Purpose: Triple-negative breast cancers (TNBC) are associated with high risk of early tumor recurrence and poor outcome. Common prognostic biomarkers give very restricted predictive information of tumor recurrences in TNBC. Human serum contains stably expressed microRNAs (miRNAs), which have been discovered to predict prognosis in patients with cancer. The purpose of this study was to identify circulating biomarkers able to predict clinical outcome in TNBC.Experimental Design: We performed genome-wide serum miRNA expression and real-time PCR analyses to investigate the ability of miRNAs in predicting tumor relapse in serum samples from 60 primary TNBC. Patients were divided into training and testing cohorts.Results: By Cox regression analysis, we identified a four-miRNA signature (miR-18b, miR-103, miR-107, and miR-652) that predicted tumor relapse and overall survival. This miRNA signature was further validated in an independent cohort of 70 TNBC. A high-risk signature score was developed and significantly associated with tumor recurrence and reduced survival. Multivariate Cox regression models indicated that the risk score based on the four-miRNA signature was an independent prognostic classifier of patients with TNBC.Conclusions: This signature may serve as a minimally invasive predictor of tumor relapse and overall survival for patients with TNBC. This prediction model may ultimately lead to better treatment options for patients with TNBC.

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“…Lessons learned from FBXW7-associated murine cancer models also convincingly demonstrated that it is a bona fide tumor suppressor gene with extensive functions [26]. Recent genetic profiles of human cancers based on high-throughput sequencing revealed that FBXW7 is among the most frequently mutated cancer genes [28][29][30][31][32][33]. Thus, FBXW7 has been illuminated to be a central mediator in tumorigenesis [34].…”

Section: Discussionmentioning

confidence: 97%