title: Copy number alterations and allelic ratio in relation to recurrence of rectal cancer.
abstract: BACKGROUND
  In rectal cancer, total mesorectal excision surgery combined with preoperative (chemo)radiotherapy reduces local recurrence rates but does not improve overall patient survival, a result that may be due to the harmful side effects and/or co-morbidity of preoperative treatment. New biomarkers are needed to facilitate identification of rectal cancer patients at high risk for local recurrent disease. This would allow for preoperative (chemo)radiotherapy to be restricted to high-risk patients, thereby reducing overtreatment and allowing personalized treatment protocols. We analyzed genome-wide DNA copy number (CN) and allelic alterations in 112 tumors from preoperatively untreated rectal cancer patients. Sixty-six patients with local and/or distant recurrent disease were compared to matched controls without recurrence. Results were validated in a second cohort of tumors from 95 matched rectal cancer patients. Additionally, we performed a meta-analysis that included 42 studies reporting on CN alterations in colorectal cancer and compared results to our own data.
  
  
  RESULTS
  The genomic profiles in our study were comparable to other rectal cancer studies. Results of the meta-analysis supported the hypothesis that colon cancer and rectal cancer may be distinct disease entities. In our discovery patient study cohort, allelic retention of chromosome 7 was significantly associated with local recurrent disease. Data from the validation cohort were supportive, albeit not statistically significant, of this finding.
  
  
  CONCLUSIONS
  We showed that retention of heterozygosity on chromosome 7 may be associated with local recurrence in rectal cancer. Further research is warranted to elucidate the mechanisms and effect of retention of chromosome 7 on the development of local recurrent disease in rectal cancer.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. I.J.Goossens-Beumer@lumc.nl.
authors.forename: Inès J
authors.initials: IJ
authors.lastname: Goossens-Beumer
authors.affiliation: Department of Pathology, L1-Q, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. J.Oosting@lumc.nl.
authors.forename: Jan
authors.initials: J
authors.lastname: Oosting
authors.affiliation: Department of Pathology, L1-Q, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. W.E.Corver@lumc.nl.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Corver
authors.affiliation: ServiceXS, Plesmanlaan 1d, Leiden, The Netherlands. marjosfrawil@gmail.com.
authors.forename: Marjolein J F W
authors.initials: MJ
authors.lastname: Janssen
authors.affiliation: ServiceXS, Plesmanlaan 1d, Leiden, The Netherlands. b.janssen@servicexs.com.
authors.forename: Bart
authors.initials: B
authors.lastname: Janssen
authors.affiliation: ServiceXS, Plesmanlaan 1d, Leiden, The Netherlands. wilbertvanworkum@gmail.com.
authors.forename: Wilbert
authors.initials: W
authors.lastname: van Workum
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. C.J.H.van_de_Velde@lumc.nl.
authors.forename: Eliane C M
authors.initials: EC
authors.lastname: Zeestraten
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. elianezeestraten@hotmail.com.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Department of Pathology, L1-Q, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. J.Morreau@lumc.nl.
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. P.J.K.Kuppen@lumc.nl.
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.affiliation: Department of Pathology, L1-Q, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. T.van_Wezel@lumc.nl.
authors.forename: Tom
authors.initials: T
authors.lastname: van Wezel
mesh_terms: D000328:Adult; D000368:Aged; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D049690:History, Ancient; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis