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. 2014 May 15;5(9):2349-54.
doi: 10.18632/oncotarget.1946.

Unique molecular signatures as a hallmark of patients with metastatic breast cancer: implications for current treatment paradigms

Jennifer J Wheler  1 , Barbara A Parker, Jack J Lee, Johnique T Atkins, Filip Janku, Apostolia M Tsimberidou, Ralph Zinner, Vivek Subbiah, Siqing Fu, Richard Schwab, Stacy Moulder, Vicente Valero, Maria Schwaederle, Roman Yelensky, Vincent A Miller, M Philip J Stephens, Funda Meric-Bernstam, Razelle Kurzrock
Affiliations

Unique molecular signatures as a hallmark of patients with metastatic breast cancer: implications for current treatment paradigms

Jennifer J Wheler et al. Oncotarget. .

Abstract

Our analysis of the tumors of 57 women with metastatic breast cancer with next generation sequencing (NGS) demonstrates that each patient's tumor is unique in its molecular fingerprint. We observed 216 somatic aberrations in 70 different genes, including 131 distinct aberrations. The most common gene alterations (in order of decreasing frequency) included: TP53, PIK3CA, CCND1, MYC, HER2 (ERBB2), MCL1, PTEN, FGFR1, GATA3, NF1, PIK3R1, BRCA2, EGFR, IRS2, CDH1, CDKN2A, FGF19, FGF3 and FGF4. Aberrations included mutations (46%), amplifications (45%), deletions (5%), splices (2%), truncations (1%), fusions (0.5%) and rearrangements (0.5%), with multiple distinct variants within the same gene. Many of these aberrations represent druggable targets, either through direct pathway inhibition or through an associated pathway (via 'crosstalk'). The 'molecular individuality' of these tumors suggests that a customized strategy, using an "N-of-One" model of precision medicine, may represent an optimal approach for the treatment of patients with advanced tumors.

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Figures

Figure 1
Figure 1
Number of Alterations seen in Patients Grouped by Hormone Receptor (HR) and HER2 Status
See this image and copyright information in PMC

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