Meeting
2014 Gastrointestinal Cancers Symposium
Molecular profiling of patients (pts) with advanced colorectal cancer (CRC): Princess Margaret Cancer Centre experience.
Authors
Joanne W. Chiu
Princess Margaret Cancer Centre, Toronto, ON, Canada
Joanne W. Chiu , Philippe L. Bedard , Michael H. Roehrl , Stefano Serra , Monika K. Kryzanowska , Jennifer J. Knox , Helen Mackay , David W. Hedley , Malcolm J. Moore , Geoffrey Liu , Neesha C. Dhani , Suzanne Kamel-Reid , Emina Torlakovic , Tao Wang , Ming-Sound Tsao , Dianne Chadwick , Tong Zhang , Celeste Yu , Eric Xueyu Chen , Shingo Sakashita
Organizations
Princess Margaret Cancer Centre, Toronto, ON, Canada, Princess Margaret Cancer Center, Toronto, ON, Canada, Biospecimen Sciences Program, University Health Network, Toronto, ON, Canada, Department of Pathology and Laboratory Medicine, University Health Network, Toronto, ON, Canada, Department of Medicine, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada, Ontario Cancer Institute; Princess Margaret Hospital, Toronto, ON, Canada, Princess Margaret Hospital, Toronto, ON, Canada, Princess Margaret Cancer Centre, Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada, Princess Margaret Cancer Center, University Health Network, Division of Medical Oncology & Hematology, Department of Medicine, University of Toronto, Toronto, ON, Canada, Department of Pathology, University Health Network, Toronto, ON, Canada, Laboratory Medicine, University Health Network, University of Toronto, Toronto, ON, Canada, Princess Margaret Cancer Center, University Health Network, Division of Medical Oncology & Hematology, Toronto, ON, Canada, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada
Research Funding
No funding sources reported
Background: The prevalence of somatic mutations other than KRAS, PIK3CA and BRAF in CRC has not been well described. This study reports molecular profiling of pts with advanced CRC in clinical practice. Methods: Pts with advanced CRC are enrolled in an ongoing institution-wide screening program. Molecular profiling is performed on FFPE archival tissues using a customized Sequenom panel (23 genes, 279 mutations) or the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons, ≥ 500x coverage) in our CLIA-certified laboratory. PTEN negative tumor is defined by IHC with H score <1. Demographic and clinical data are collected. Data was analyzed by chi-square test. Results: From March 2012 to August 2013, 132 pts were enrolled. One or more mutations were found in 50% (58/117) and 93%(14/15) of pts using Sequenom and MiSeq platforms respectively. Mutation rate was 40% for KRAS, 9% for PIK3CA, 2% for BRAF, 4% for NRAS, and 1% for each of CTNNB1, ERBB2, FGFR3, and EGFR. Mutations outside of codons 12/13 were found in 8% (4/53) of tumors with KRAS mutations. MiSeq showed additional mutations including ERBB4 (1/15), SMAD4 (1/15), FRXW7 (1/5), APC (5/15), and TP53 (12/15) in CRC. Co-mutation with KRAS was found in 58% (7/12) of pts with PIK3CA mutation and 80% (4/5) of pts with APC mutation. PTEN negative tumor was present in 20% (11/55) of pts. Presence of any mutation was significantly more common for pts with right-sided CRC (73%) compared to those with left-sided CRC (47%) and rectal CRC (38%) (p < 0.01). There was a trend toward increased proportion of KRAS mutation in right-sided CRC (p=0.06). There was no difference in age, ethnicity, gender, smoking status, stage at presentation, pathology grade, and response to first-line chemotherapy between right and left-sided CRC. Conclusions: Somatic alterations are common in advanced CRC. Targeted next-generation DNA sequencing identifies additional clinically relevant alterations than multiplex genotyping. Differences in the mutation profile of right and left-sided CRC tumors should be further investigated. Updated results will be presented at the meeting.
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Abstract Details
Session Type
Poster Session
Session Title
General Poster Session C: Cancers of the Colon and Rectum
Track
Cancers of the Colon, Rectum, and Anus
Sub Track
Translational Research
Citation
J Clin Oncol 32, 2014 (suppl 3; abstr 459)
DOI
10.1200/jco.2014.32.3_suppl.459
Abstract #
459
Poster Bd #
B22
Abstract Disclosures
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