Abstract 4709: Extensive intratumor proteogenomic heterogeneity revealed by multiregion sampling in a high-grade serous ovarian tumor specimen

Hunt, Allison L.; Bateman, Nicholas W.; Wang, Guisong; Parikh, Niyati; Oliver, Julie A.; Mitchell, D. L.; Gist, Glenn; Hood, Brian L.; Zhou, Ming; Blanton, Brian; Conrads, Kelly A.; Hamilton, Chad A.; Darcy, Kathleen; Shriver, Craig D.; Casablanca, Yovanni; Maxwell, G. Larry; Conrads, Thomas P.

doi:10.1158/1538-7445.sabcs18-4709

Cited by 2 publications

(1 citation statement)

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“…Use of cryopulverized bulk tumor material improved the depth and internal concordance of molecular analysis but sacrificed architectural information and the cellular resolution afforded by methods such as imaging mass cytometry ( Jackson et al, 2020 ). Higher spatial resolution could be achieved by approaches optimized for smaller amounts of input material ( Hunt et al, 2019 ; Satpathy et al, 2020 ) or thoughtful integration of single-cell genomics and proteomics. The type of associations described throughout this manuscript are hypothesis generating and therefore cannot be understood in terms of firm biological conclusions or direct evidence of specific therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

Krug

Jaehnig

Satpathy

et al. 2020

Cell

333

334

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SUMMARY The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this “proteogenomics” approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases.Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy.

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Section: Discussionmentioning

confidence: 99%

Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

Krug

Jaehnig

Satpathy

et al. 2020

Cell

333

334

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Laser Capture Proteomics: spatial tissue molecular profiling from the bench to personalized medicine

Liotta

Pappalardo

Carpino

et al. 2021

Expert Review of Proteomics

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Introduction: Laser Capture Microdissection (LCM) uses a laser to isolate, or capture, specific cells of interest in a complex heterogeneous tissue section, under direct microscopic visualization. Recently, there has been a surge of publications using LCM for tissue spatial molecular profiling relevant to a wide range of research topics. Areas Covered: We summarize the many advances in tissue Laser Capture Proteomics (LCP) using mass spectrometry for discovery, and protein arrays for signal pathway network mapping. This review emphasizes: a) transition of LCM phosphoproteomics from the lab to the clinic for individualized cancer therapy, and b) the emerging frontier of LCM single cell molecular analysis combining proteomics with genomic, and transcriptomic analysis. The search strategy was based on the combination of MeSH terms with expert refinement. Expert Opinion: LCM is complemented by a rich set of instruments, methodology protocols, and analytical A.I. (artificial intelligence) software for basic and translational research. Resolution is advancing to the tissue single cell level. A vision for the future evolution of LCM is presented. Emerging LCM technology is combining digital and AI guided remote imaging with automation, and telepathology, to a achieve multi-omic profiling that was not previously possible.

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Abstract 4709: Extensive intratumor proteogenomic heterogeneity revealed by multiregion sampling in a high-grade serous ovarian tumor specimen

Cited by 2 publications

References 0 publications

Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

Laser Capture Proteomics: spatial tissue molecular profiling from the bench to personalized medicine

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