Allelotyping identification of genomic alterations in rectal chromosomally unstable tumors without preoperative treatment.
BACKGROUND
Numerous studies reported genomic alterations in colorectal human tumors but few focused on rectal tumors with the specification of preoperative-treated or untreated tumors. The goals of this study were to list chromosome allelic imbalances and correlate their frequency with tumor progression and to identify potential molecular markers of progression in rectal chromosomally unstable tumors without preoperative treatment.


METHODS
Genomic alterations of 57 rectal tumors assessed by allelotyping targeting 33 chromosomal loci, were clusterised and compared to those of 151 left colon tumors.


RESULTS
Clustering separated the rectal tumors without preoperative treatment into three subtypes according to the allelic imbalance frequency and genomic alteration associations. The tumors without preoperative treatment displayed a significantly higher allelic imbalance frequency (54%) than the tumors with preoperative treatment (33%), suggesting that treatment could target highly altered tumor clones. Interestingly, the survival analysis identified three potential prognostic molecular survival markers, D1S197, D5S430, and D14S65, for tumors without preoperative treatment.


CONCLUSIONS
Based on the genomic status of 33 chromosomal loci, we observed that rectal tumors without preoperative treatment segregate according to the global allelic imbalance frequency but without correlation to the tumor progression. Moreover, the detailed associations of alterations in rectal tumors are different from those described in colon tumors suggesting that rectal and left tumors should be considered as separate entities. Finally, potential prognostic genomic molecular markers for survival are proposed which status could specify the clinical course of the tumors.
Romain
Benoît
B
Service de Chirurgie Générale et Digestive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Avenue Molière, 67098 Strasbourg Cedex, France. benoit.romain@chru-strasbourg.fr
Neuville
Agnès
A
Meyer
Nicolas
N
Brigand
Cécile
C
Rohr
Serge
S
Schneider
Anne
A
Gaub
Marie-Pierre
MP
Guenot
Dominique
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D012004:Rectal Neoplasms / Q000235:genetics* / Q000601:surgery*; D016896:Treatment Outcome