TY - JOUR
T1 - Biological validation of RNA sequencing data from formalin- fixed paraffin-embedded primary melanomas
AU - Kwong, Lawrence N.
AU - De Macedo, Mariana Petaccia
AU - Haydu, Lauren
AU - Joon, Aron Y.
AU - Tetzlaff, Michael T.
AU - Calderone, Tiffany L.
AU - Wu, Chiang Jun
AU - Kwong, Man Kam
AU - Roszik, Jason
AU - Hess, Kenneth R.
AU - Davies, Michael A.
AU - Lazar, Alexander J.
AU - Gershenwald, Jeffrey E.
N1 - Publisher Copyright:
© 2019 American Society of Clinical Oncology.
PY - 2018
Y1 - 2018
N2 - Purpose Initiatives such as The Cancer Genome Atlas and International Cancer Genome Consortium have generated high-quality, multiplatform molecular data from thousands of frozen tumor samples. Although these initiatives have provided invaluable insight into cancer biology, a tremendous potential resource remains largely untapped in formalin-fixed, paraffin-embedded (FFPE) samples that are more readily available but which can present technical challenges because of crosslinking of fragile molecules such as RNA. Materials and Methods We extracted RNA from FFPE primary melanomas and assessed two gene expression platforms-genome-wide RNA sequencing and targeted NanoString- for their ability to generate coherent biologic signals. To do so, we generated an improved approach to quantifying gene expression pathways. We refined pathway scores through correlation-guided gene subsetting. We also make comparisons to The Cancer Genome Atlas and other publicly available melanoma datasets. Results The comparison of the gene expression patterns to each other, to established biologic modules, and to clinical and immunohistochemical data confirmed the fidelity of biologic signals from both platforms using FFPE samples to known biology. Moreover, correlations with patient outcome data were consistent with previous frozen-tissue- based studies. Conclusion FFPE samples from previously difficult-to-access cancer types, such as small primary melanomas, represent a valuable and previously unexploited source of analyte for RNA sequencing and NanoString platforms. This work provides an important step toward the use of such platforms to unlock novel molecular underpinnings and inform future biologically driven clinical decisions.
AB - Purpose Initiatives such as The Cancer Genome Atlas and International Cancer Genome Consortium have generated high-quality, multiplatform molecular data from thousands of frozen tumor samples. Although these initiatives have provided invaluable insight into cancer biology, a tremendous potential resource remains largely untapped in formalin-fixed, paraffin-embedded (FFPE) samples that are more readily available but which can present technical challenges because of crosslinking of fragile molecules such as RNA. Materials and Methods We extracted RNA from FFPE primary melanomas and assessed two gene expression platforms-genome-wide RNA sequencing and targeted NanoString- for their ability to generate coherent biologic signals. To do so, we generated an improved approach to quantifying gene expression pathways. We refined pathway scores through correlation-guided gene subsetting. We also make comparisons to The Cancer Genome Atlas and other publicly available melanoma datasets. Results The comparison of the gene expression patterns to each other, to established biologic modules, and to clinical and immunohistochemical data confirmed the fidelity of biologic signals from both platforms using FFPE samples to known biology. Moreover, correlations with patient outcome data were consistent with previous frozen-tissue- based studies. Conclusion FFPE samples from previously difficult-to-access cancer types, such as small primary melanomas, represent a valuable and previously unexploited source of analyte for RNA sequencing and NanoString platforms. This work provides an important step toward the use of such platforms to unlock novel molecular underpinnings and inform future biologically driven clinical decisions.
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U2 - 10.1200/PO.17.00259
DO - 10.1200/PO.17.00259
M3 - Article
C2 - 31058252
AN - SCOPUS:85066750433
SN - 2473-4284
VL - 2
SP - 1
EP - 19
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -