Dataset Information

Proteogenomics of colorectal cancer liver metastases

ABSTRACT: Colorectal cancer (CRC) is the third most common and second most deadly cancer worldwide. Treatments for metastatic CRC (mCRC) are still largely based on toxic chemotherapy regimens, but important insights into tumor biology enabled the development of targeted cancer therapies. Here, we describe a proteogenomic analysis of CRC liver metastases (metastatic CRC, mCRC), an ideal setting to analyze therapeutic resistance which occurs in a short time frame. We selected liver metastases from two CRC patients on both of which we performed deep proteome profiling and WES and RNAseq-directed database searches, identifying 10 predicted muttaions, one of which was KRAS G12V. finding we generated targeted parallel reaction monitoring (PRM) assays using stable isotope labelled standard (SIS) peptides to quantify the actual concentration (fmol per µg of total protein) of the mutated and canonical (wildtype) protein variants for 8 different mutations. We demonstrate on a total of 8 tumor and 6 paired healthy tissue samples (7 and 6 out of these KRASG12V) that PRM allows quantifying the actual mutation rate on the protein level from as little 10 µg of total protein starting amount and within a single 1 hour nano-LC-MS/MS run.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

DISEASE(S): Colorectal Cancer

SUBMITTER: Bernhard Blank-Landeshammer

LAB HEAD: Albert Sickmann

PROVIDER: PXD014222 | Pride | 2019-12-04

REPOSITORIES: Pride

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Publications

Proteogenomics of Colorectal Cancer Liver Metastases: Complementing Precision Oncology with Phenotypic Data.

Blank-Landeshammer Bernhard B Richard Vincent R VR Mitsa Georgia G Marques Maud M LeBlanc André A Kollipara Laxmikanth L Feldmann Ingo I Couetoux du Tertre Mathilde M Gambaro Karen K McNamara Suzan S Spatz Alan A Zahedi René P RP Sickmann Albert A Batist Gerald G Borchers Christoph H CH

Cancers 20191201 12

: Hotspot testing for activating KRAS mutations is used in precision oncology to select colorectal cancer (CRC) patients who are eligible for anti-EGFR treatment. However, even for KRASwildtype tumors anti-EGFR response rates are <30%, while mutated-KRAS does not entirely rule out response, indicating the need for improved patient stratification. We performed proteogenomic phenotyping of KRASwildtype and KRASG12V CRC live ...[more]

PMID: 31805664

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			Action	DRS
	Lumos04010.raw	Raw
	QExactiveHF02_06090.raw	Raw
	Sample_2-135-4_MSGF_WES.xlsx	Xlsx
	Sample_2-135_4_TiO2.msf	Msf
	Sample_2-135_4_TiO2.pep.xml	Pepxml