Volume 126, Issue 3, Pages (March 2004)

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Volume 126, Issue 3, Pages 64-659 (March 2004) Loss of activin receptor type 2 protein expression in microsatellite unstable colon cancers  Barbara Jung, Ryan T. Doctolero, Akihiro Tajima, Alexie K. Nguyen, Temitope Keku, Robert S. Sandler, John M. Carethers  Gastroenterology  Volume 126, Issue 3, Pages 64-659 (March 2004) DOI: 10.1053/j.gastro.2004.01.008

Figure 1 Frameshift mutation of the polyadenine (A8) tract in exon 10 of ACVR2 in MSI-H colon cancers. Seven representative MSI-H tumors are shown. Matching normal (n) and tumor (t) DNA was amplified using specific primers surrounding the A8 tract of exon 10 of ACVR2 and electrophoresed in adjacent lanes. A downward shift in band indicative of a deletion of one adenine in tumors is marked with asterisks. Tumors with both A8 and A7 alleles could be heterozygous for both wild-type and mutant alleles, or their DNA contains mixed tumor and nontumor cell populations. Gastroenterology 2004 126, 64-659DOI: (10.1053/j.gastro.2004.01.008)

Figure 2 DNA sequences of the exon 10 polyadenine tract of ACVR2 in MSS and MSI-H tumors. (A) Representative MSS tumor showing only wild-type T8 in the reverse strand. (B) Representative MSI-H tumor that showed a frameshift on the polyacrylamide gel (Figure 1) has a 1-base pair contraction to T7 in the reverse strand. Gastroenterology 2004 126, 64-659DOI: (10.1053/j.gastro.2004.01.008)

Figure 3 ACVR2 protein expression in MSI-H colon tumors. Tumors were incubated with an ACVR2 antibody that targeted near the carboxyl terminus of the receptor, beyond the predicted truncation from a frameshift mutation within exon 10. (A and B) Examples of MSI-H tumors that showed ACVR2 frameshift mutation. Note the expression of ACVR2 protein in normal colonic epithelium and loss of expression in the adenocarcinoma. (C) MSI-H tumor with mutated ACVR2 showing loss of protein expression within subpopulations of the tumor only. (D) MSI-H tumor with wild-type ACVR2 expressing ACVR2 protein in both normal and tumor tissue. Gastroenterology 2004 126, 64-659DOI: (10.1053/j.gastro.2004.01.008)