Genomic variation as a marker of response to neoadjuvant therapy in locally advanced rectal cancer.
Document Type
Article
Publication Date
1-1-2020
Publication Title
Molecular & cellular oncology
Abstract
There is variation in the responsiveness of locally advanced rectal cancer to neoadjuvant chemoradiation, from complete response to total resistance. This study compared genetic variation in rectal cancer patients who had a complete response to chemoradiation versus poor response, using tumor tissue samples sequenced with genomics analysis software. Rectal cancer patients treated with chemoradiation and proctectomy June 2006-March 2017 were grouped based on response to chemoradiation: those with no residual tumor after surgery (CR, complete responders, AJCC-CPR tumor grade 0, n = 8), and those with poor response (PR, AJCC-CPR tumor grade two or three on surgical resection, n = 8). We identified 195 variants in 83 genes in tissue specimens implicated in colorectal cancer biopathways. PR patients showed mutations in four genes not mutated in complete responders: KDM6A, ABL1, DAXX-ZBTB22, and KRAS. Ten genes were mutated only in the CR group, including ARID1A, PMS2, JAK1, CREBBP, MTOR, RB1, PRKAR1A, FBXW7, ATM C11orf65, and KMT2D, with specific discriminating variants noted in DMNT3A, KDM6A, MTOR, APC, and TP53. Although conclusions may be limited by small sample size in this pilot study, we identified multiple genetic variations in tumor DNA from rectal cancer patients who are poor responders to neoadjuvant chemoradiation, compared to complete responders.
Volume
7
Issue
3
First Page
1716618
Last Page
1716618
Recommended Citation
Douglas JK, Callahan RE, Hothem ZA, Cousineau CS, Kawak S, Thibodeau BJ, Bergeron S, Li W, Peeples CE, Wasvary HJ. Genomic variation as a marker of response to neoadjuvant therapy in locally advanced rectal cancer. Mol Cell Oncol. 2020 Mar 2;7(3):1716618. doi: 10.1080/23723556.2020.1716618. PMID: 32391418; PMCID: PMC7199754.
DOI
10.1080/23723556.2020.1716618
ISSN
2372-3556
PubMed ID
32391418