Annals of Oncology Advance Access originally published online on October 25, 2005
Annals of Oncology 2006 17(1):43-49; doi:10.1093/annonc/mdj017
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© 2005 European Society for Medical Oncology
Allelic loss analysis of early-stage flat-type colorectal tumors
Departments of 1 Surgery (I), 2 Gastroenterology and 4 Pathology (II), Juntendo University, Tokyo; 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; 5 Pathology and Clinical Laboratory Divisions, National Cancer Center Research Institute and Hospital, Tokyo, Japan
* Correspondence to: Dr H. Fujii, Department of Pathology (II), Juntendo University School of Medicine, 2-1-1 Hongo, Tokyo 113-8421, Japan. Tel: +81-3-5802-1039; Fax: +81-3-5684-1646; E-mail: hfujii{at}med.juntendo.ac.jp
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.
Key words: flat-type colorectal tumor, fractional allelic loss, loss of heterozygosity, tumor suppressor gene, 17p, 18p, 18q, 22q