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Annals of Oncology Advance Access published online on October 25, 2005
Annals of Oncology, doi:10.1093/annonc/mdj017
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© 2005 European Society for Medical Oncology
Received April 3, 2005
Revised August 7, 2005
Accepted August 8, 2005

original article

Allelic loss analysis of early-stage flat-type colorectal tumors

H. Orita 1, N. Sakamoto 2, Y. Ajioka 3, T. Terai 2, O. Hino 4, N. Sato 2, T. Shimoda 5, T. Kamano 1, M. Tsurumaru 1, and H. Fujii 4*

1 Department of Surgery (I), Juntendo University, Tokyo, Japan
2 Department of Gastroenterology, Juntendo University, Tokyo, Japan
3 Division of Molecular & Cellular Medicine, Department of Molecular Genetics, Course for Molecular & Cellular Medicine, Niigata University, Graduate School of Medical & Dental Science, Niigata City, Japan
4 Department of Pathology (II), Juntendo University, Tokyo, Japan
5 Pathology and Clinical Laboratory Divisions, National Cancer Center Research Institute and Hospital, Tokyo, Japan

* To whom correspondence should be addressed.
H. Fujii, E-mail: hfujii{at}med.juntendo.ac.jp


  Abstract

Background: Flat-type colorectal tumors are rare, but are known for their unusual flat morphology and aggressive clinical behavior despite their small size. To identify distinct genetic alterations, loss of heterozygosity (LOH) analysis was performed on microdissected tissues.

Materials and methods: DNA was extracted from multiple microdissected foci in 43 cases of early-stage flat-type colorectal tumors and LOH analysis was performed on 2q, 4q, 5q, 12q, 14q, 15q, 17p, 18q, 18p and 22q.

Results: LOH patterns were detected in one of two forms: (i) homogeneous LOH throughout the microdissected foci, which indicated the early acquisition of LOH; and (ii) heterogeneous LOH, which were detected in a part of analyzed foci. Homogeneous and heterogeneous LOH were most frequently detected on 17p (92%) followed by 18q (81%), 18p (81%), 5q (61%), 22q (51%), 14q (44%), 15q (41%), 2q (39%), 12q (36%) and 4q (32%). Homogeneous LOH was detected most frequently on 17p (68%) followed by 18p (53%), 18q (53%), 22q (34%) and 12q (27%). The average fractional allelic loss (FAL) for heterogeneous and homogeneous LOH was 0.57 and the average FAL for homogeneous LOH was 0.37.

Conclusions: Early flat-type colorectal tumors frequently shows the early occurrence of multiple LOH including 17p, 18p, 18q and 22q, which is coupled with additional LOH of other loci either simultaneously or in the early clonal progression phase. The extent and sequences of LOH may be the mechanisms responsible for the aggressive clinical behaviors of these tumors.

Keywords: flat-type colorectal tumor; fractional allelic loss; loss of heterozygosity; tumor suppressor gene; 17p; 18p; 18q; 22q.
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