TY - JOUR
T1 - Intra-tumoral genomic heterogeneity in rectal cancer
T2 - Mutational status is dependent on preoperative biopsy depth and location
AU - Vuijk, Floris A.
AU - van de Water, Carlijn
AU - Lent-Van Vliet, Shannon
AU - van der Valk, Maxime J.M.
AU - Simmer, Femke
AU - van de Velde, Cornelis J.H.
AU - Vahrmeijer, Alexander L.
AU - Nagtegaal, Iris D.
AU - Hilling, Denise E.
N1 - 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.
PY - 2021/5/9
Y1 - 2021/5/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85105409619&partnerID=8YFLogxK
U2 - 10.3390/cancers13092271
DO - 10.3390/cancers13092271
M3 - Article
AN - SCOPUS:85105409619
VL - 13
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 9
M1 - 2271
ER -
