Intra-tumoral genomic heterogeneity in rectal cancer: Mutational status is dependent on preoperative biopsy depth and location

Floris A. Vuijk, Carlijn van de Water, Shannon Lent-Van Vliet, Maxime J.M. van der Valk, Femke Simmer, Cornelis J.H. van de Velde, Alexander L. Vahrmeijer, Iris D. Nagtegaal, Denise E. Hilling*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)


Neoadjuvant therapy before surgical resection is indicated for patients with locally advanced rectal cancer. However, a significant number of patients show minimal or no response to neoadjuvant therapy. Unfortunately, we are currently unable to predict response and identify non-responding patients before neoadjuvant treatment is given. Genomic mutational status might provide valuable prognostic information. However, it is unclear whether predictions based on genomic mutational status in single preoperative biopsies are reliable due to intra-tumoral heterogeneity. In this study we aim to investigate the reliability of genomic mutations found in single pre-operative biopsies by comparing genomic mutations to four other locations within the same tumor using next generation sequencing. Rectal cancer patients undergoing primary resection without neoadjuvant therapy were included. From each patient, one biopsy, two deep and two superficial samples were obtained and sequenced using a targeted next generation sequencing gene panel. Concordance between these five samples was assessed. In this feasibility study we included 11 patients. In 7 out of 11 (64%) patients, all 5 samples showed concordant mutations. In 4 out of 11 patients (36%) discordant mutations were observed. In conclusion, assessment of mutational status on a single pre-operative biopsy shows discordance with tumor tissue from other locations in 36% of cases. These results warrant careful interpretation of biopsy material analysis, as these might be influenced by tumor heterogeneity.

Original languageEnglish
Article number2271
Issue number9
Publication statusPublished - 9 May 2021

Bibliographical note

Funding Information:
Funding: This research was funded by the Dutch Cancer Society (Bas Mulder Award), grant number UL2015-7966 to D.E. Hilling.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


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