Volume 125, Issue 5, Pages 1330-1340 (November 2003) The genomic damage estimated by arbitrarily primed PCR DNA fingerprinting is useful for the prognosis of gastric cancer  Koichi Suzuki, Sumiko Ohnami, Chikako Tanabe, Hiroki Sasaki, Jun Yasuda, Hitoshi Katai, Kimio Yoshimura, Masaaki Terada, Manuel Perucho, Teruhiko Yoshida  Gastroenterology  Volume 125, Issue 5, Pages 1330-1340 (November 2003) DOI: 10.1016/j.gastro.2003.07.006

Figure 1 Autoradiograms of the AP-PCR DNA fingerprinting generated by arbitrary primers BLUE and MCG1 with 100 ng of genomic DNA isolated from normal (N) and tumor (T) tissues from the gastric cancer patients indicated at the top. The figure shows duplicate and triplicate analyses. Samples were amplified in independent AP-PCR experiments and analyzed in different electrophoreses. Letters at left indicate bands of known chromosomal origin. Many of the double bands represent the 2 strands of the same DNA fragment and thus were considered as only 1 band (for instance, bands J, K, L, and M of the BLUE primer). Band intensity changes are indicated by an open triangle (loss) and a closed triangle (gain). Numbers at the bottom indicate the total number of bands showing loss (−) or gain (+) in the fingerprints shown in the figure. The regions delimited by the open rectangles are magnified in the larger images shown at the bottom. The number of alterations in the tumors displayed may not match the number of alterations listed in Table 1 because the figure does not show the entire fingerprints. Gastroenterology 2003 125, 1330-1340DOI: (10.1016/j.gastro.2003.07.006)

Figure 2 Distribution of chromosomal alterations in the 74 tumors aligned by increasing number of alterations. (A) Bands corresponding to an unknown chromosomal location12,15 are not shown. Grayscales of boxes show different numbers of alterations in different bands assigned to the same chromosome. More than 1 alteration is shown as dark gray, 1 alteration as light gray, and no alteration as white. (B) Percentage of altered bands. Bands corresponding to unknown chromosomal location are included. A continuous increase in the number of chromosomal alterations was seen in this tumor series for both gains (top) and losses (bottom). Note that the order of tumors is different for gains and losses (C). (C) Distribution of alterations (both gains and losses) in the tumor series, with tumors ordered by increasing GDF values. The order of tumors is the same as in Table 1. Gastroenterology 2003 125, 1330-1340DOI: (10.1016/j.gastro.2003.07.006)

Figure 3 (A) Comparison of chromosomal imbalance detected by AP-PCR fingerprinting and CGH in 30 cases selected from each group divided by the average GDF score, excluding those with insufficient DNA stock: 17 cases with GDF scores <0.22 and 13 cases with GDF scores >0.27. IGF1R, insulin-like growth factor 1 receptor; ERBB2, v-erb-b2 erythroblastic leukemia viral oncogene homologue 2, neuro/glioblastoma-derived oncogene homologue (avian); CCNE1, cyclin E1; CPSB, cathepsin B (CTSB); PAK1, p21/Cdc42/Rac1-activated kinase 1; MET, met proto-oncogene (hepatocyte growth factor receptor); CBFA2, core-binding factor, Runt domain, α subunit 2; KRAS2, v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue; MYCL1, v-myc myelocytomatosis viral oncogene homologue, lung carcinoma derived; MLL, myeloid/lymphoid or mixed-lineage leukemia (trithorax homologue, Drosophila). (B) Genomic array image showing amplifications of gene targets (ERRB2; green) in case 3801 (left) and ratio data results in case 3801 (right). (C) Increase of intensity in band R0 (chromosome 17) detected by AP-PCR fingerprinting in case 3801. Gastroenterology 2003 125, 1330-1340DOI: (10.1016/j.gastro.2003.07.006)

Figure 4 (A) Percentage of altered bands. An arrow shows the average GDF. Black bars indicate noncurative cases, and white bars indicate curative cases. (B) Kaplan-Meier survival curves according to GDF values in each group. Curves are drawn for total cases (left), curative cases (middle), and noncurative cases (right). Gastroenterology 2003 125, 1330-1340DOI: (10.1016/j.gastro.2003.07.006)

Figure 5 (A) The distribution of chromosomal alterations aligned by increasing number of alterations according to MSI status. Bands corresponding to unknown chromosomal location are not shown. Grayscales of boxes show different numbers of alteration in different bands assigned to the same chromosome. More than 2 alterations are shown as a dark gray box, 1 alteration as a gray box, and no alterations as an empty box. The line draws a partition into 2 groups—above or below the cutoff point of 0.22 for the average GDF for MSI-negative tumors and 0.14 for MSI-positive tumors. (B) Percentage of altered bands. An arrow shows the average GDF in each group. (C) Kaplan-Meier survival curves according to the GDF values in each group. Curves are drawn for MSI-positive cases (left), total cases (middle), and MSI-negative cases (right). Gastroenterology 2003 125, 1330-1340DOI: (10.1016/j.gastro.2003.07.006)