44P - Calculated numerical karyotype with ultra low-coverage whole genome sequencing undercovers recurrent chromosomal aberrations in resectable colorectal cancer

Background

Chromosomal analysis is an established method with therapeutic and prognostic relevance in some hematologic malignancies. Its role in solid tumors is yet to be defined. In this study we aimed to analyze numerical chromosomal aberrations in colorectal cancer using an ultra low-coverage whole genome sequencing (ulcWGS) method which we previously used in other reports.

Methods

We analyzed FFPE samples of 62 patients with resectable colorectal cancer referred to our center between 2000 and 2004. We extracted DNA and created ulcWGS libraries using the NEBNext Ultra II Kit as previously described. Sequencig was conducted on a Miseq Instrument and output from raw data was generated using the proprietary software CORIANDR. Data analysis was performed using Excel and GraphPad Prism.

Results

15/62 patients had numerically normal karyotype, 13/62 had 1-2 numerical aberrations and 34/62 had 3 or more. 22/62 had trisomies and 24/62 had monosomies. The most common monosomies were loss of chromosome 14, 15, 18 and Y, whereas the most common trisomies were amplification of chromosome 7, 13 and 20. High level ERBB2 amplification was identified in 2 patients. Normal karyotype was not associated with prolonged overall survival.

Conclusions

In this study we used a low-throughput sequencing technology and obtained results comparable with those available in the literature using cytogenetic analyses on colorectal cancer. The presence of an abnormal numerical karyotype is a common event in colorectal cancer which does not appear to influence prognosis. The effect of specific copy number alterations, especially in the context of concomitant gene mutations (e.g. KRAS and PIK3CA), needs to be further investigated.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Mack: Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Invited Speaker: Roche, Boehringer Ingelheim. All other authors have declared no conflicts of interest.