Genomic analysis of early adenocarcinoma of the esophagus or gastroesophageal junction: tumor progression is associated with alteration of 1q and 8p sequences.
Early (T1 stage) adenocarcinoma of the esophagus or gastroesophageal junction is a potentially curable disease. We analyzed the genomic spectra of 33 early neoplastic lesions after subdividing the tumors into six depths of invasion (T1-mucosal, m1-m3; T1-submucosal, sm1-sm3). Two subgroups were defined, T1m1-sm1 (n = 18) and T1sm2-sm3 (n = 15). The latter group is associated with frequent lymphatic spread and a high percentage of local and/or distant recurrence. Comparative genomic hybridization with a genomewide 3,500-element BAC-PAC array revealed a characteristic gastroesophageal adenocarcinoma pattern of changes, with losses on chromosome arms 4pq, 5q, 8p, 9p, 17p, and 18q and gains on 1q, 6p, 7pq, 11q, 15q, 17q, and 20pq. However, when the two groups were compared, the following BAC clones showed significantly more alterations in the T1sm2-sm3 group: RP11-534L20 (1q32.1) and RP11-175A4 (6p21.32), showing gains, and RP11-356F24, RP11-433L7, and RP11-241P12 (all at 8p), showing losses. Gain of RP11-534L20 (1q32.1) and loss of RP11-433L7 (8p22) were associated not only with a recurrence-free period (P = 0.0007 and 0.007, respectively), but also with regional lymphatic dissemination (P = 0.005 and 0.003, respectively). These DNA clones can be considered genomic markers for the aggressive behavior of early esophageal and gastroesophageal junction adenocarcinoma.
Department of Pathology, Erasmus MC University Medical Center, Josephine Nefkens Institute, Rotterdam, The Netherlands. h.vandekken@erasmusmc.nl
Herman
H
van Dekken
Josiane C
JC
Wink
Kees J
KJ
Vissers
Ronald
R
van Marion
Linetta B
LB
Koppert
Hugo W
HW
Tilanus
Peter D
PD
Siersema
Hans J
HJ
Tanke
Karoly
K
Szuhai
Wim C J
WC
Hop
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002898:Chromosomes, Human, Pair 8; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization