Microsatellite instability in gastric MALT lymphomas and other associated neoplasms

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      Background: Microsatellite instability (MSI), caused by a reduced efficacy of the DNA mismatch repair (MMR) machinery, represents a type of genomic instability frequently detected in HNPCC spectrum cancers and in a subset of sporadic carcinomas. The involvement of MSI in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) has never been conclusively investigated. In this study, we tested the presence of MSI in tumor samples of patients harboring both MALT lymphomas and other types of malignancies.
      Materials and methods: We examined 10 microsatellite loci (D3S11, D3S1261, D3S1265, D6S262, D6S193, BAT-26, BAT-25, D17S250, APC, D2S123) out of a total of 34 primary tumors from 14 patients with MALT lymphomas and one or more additional neoplasms. The patients' MSI results were also tested for an association with a positive family history of cancer.
      Results: MSI, defined by the presence of microsatellite alterations in more than 40% of the examined loci, was scored negative in all tumors studied, and pedigree analysis failed to identify any condition of familial cancer among the patients examined.
      Conclusions: The present study suggests that defects in DNA mismatch repair do not contribute significantly to the molecular pathogenesis of MALT lymphomas and associated neoplasms.

      Key words


        • Isaacson P.C.
        The MALT lymphoma concept update.
        Ann Oncol. 1995; 6: 319-320
        • Zucca E.
        • Bertoni F.
        • Roggero E.
        • et al.
        Molecular analysis of the progression from Helicobacter pylori-associated chronic gastritis to mucosa-associated lymphoid-tissue lymphoma of the stomach.
        N Engl J Med. 1998; 338: 804-810
        • Wotherspoon A.C.
        • Pan L.
        • Diss T.C.
        • et al.
        Cytogenetic study of B-cell lymphoma of mucosa-associated lymphoid tissue.
        Cancer Genet Cytogenet. 1992; 58: 35-38
        • Clark H.M.
        • Jones D.B.
        • Wright D.H.
        Cytogenetic and molecular genetic studies of the t(14;18) and t(14;19) in nodal and extranodal B-cell lymphoma.
        J Pathol. 1992; 166: 129-137
        • Whang-Peng J.
        • Knutsen T.
        • Jaffe E.
        • et al.
        Cytogenetic study of two cases with lymphoma of mucosa-associated lymphoid tissue.
        Cancer Genet Cytogenet. 1994; 77: 74-80
        • Wotherspoon A.C.
        • Finn T.M.
        • Isaacson P.G.
        Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue.
        Blood. 1995; 85: 2000-2004
        • Ott G.
        • Kalla J.
        • Steinhoff A.
        • et al.
        Trysomy 3 is not a common feature in malignant lymphomas of mucosa-associated lymphoid tissue type.
        Am J Pathol. 1998; 153: 689-694
        • Ott G.
        • Katzenberger T.
        • Greiner A.
        • et al.
        The t(11;18)(q21;q21) chromosome traslocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin’s lymphomas of the mucosa-associated lymphoid tissue (MALT) type.
        Cancer Res. 1997; 57: 3944-3948
        • Liang R.
        • Chan W.P.
        • Kwong Y.L.
        • et al.
        Mutation of the 5’ non-coding region of the bcl-6 gene in low-grade gastric lymphoma of the mucosa-associated lymphoid tissue.
        Cancer Genet Cytogenet. 1998; 102: 110-113
        • Aaltonen L.
        • Peltomaki P.
        • Leach F.S.
        • et al.
        Clues to the pathogenesis of familial colorectal cancer.
        Science. 1993; 260: 812-816
        • Han H-J
        • Yanagisawa A.
        • Kato Y.
        • et al.
        Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer.
        Cancer Res. 1993; 53: 5087-5089
        • Peltomaki P.
        • Lothe R.A.
        • Aaltonen L.
        • et al.
        Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome.
        Cancer Res. 1993; 53: 5853-5855
        • Eshleman J.R.
        • Markowitz S.D.
        Microsatellite instability in inherited and sporadic neoplasms.
        Curr Opin Oncol. 1995; 7: 83-89
        • Horii A.
        • Han H-J
        • Mamoru S.
        • et al.
        Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers.
        Cancer Res. 1994; 54: 3373-3375
        • Gamberi B.B.
        • Gaidano G.
        • Parsa N.
        • et al.
        Microsatellite instability is rare in B-cell non-Hodgkin’s lymphomas.
        Blood. 1997; 89: 975-979
        • Fey M.F.
        Microsatellite markers in leukaemia and lymphoma: Comments on a timely topic.
        Leuk Lymph. 1997; 28: 11-22
        • Peng H.
        • Chen G.
        • Du M.
        • et al.
        Replication error phenotype and p53 gene mutation in lymphomas of mucosa-associated lymphoid tissue.
        Am J Pathol. 1996; 148: 643-648
        • Du M.
        • Isaacson P.G.
        Recent advances in our understanding of the biology and pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma.
        FORUM. 1998; 8: 162-173
        • Zucca E.
        • Pinotti G.
        • Roggero E.
        • et al.
        High incidence of other neoplasms in patient with low-grade gastric MALT lymphoma.
        Ann Oncol. 1995; 6: 726-728
        • Isaacson P.G.
        Gastrointestinal lymphoma.
        Hum Pathol. 1994; 25: 1020-1029
        • Calvert R.
        • Randerson J.
        • Evans P.
        • et al.
        Genetic abnormalities during transition from Helicobacter-pylori-associated gastritis to low-grade MALToma.
        Lancet. 1995; 345: 26-27
        • Xu W.S.
        • Chan A.C.L.
        • Liang R.
        • et al.
        No evidence of replication error phenotype in primary gastric lymphoma of mucosa-associated lymphoid tissue.
        Int J Cancer. 1998; 76: 635-638
        • Tibiletti M.G.
        • Furlan D.
        • Taborelli M.
        • et al.
        Microsatellite instability in endometrial cancer: Relation to histological subtypes.
        Gynecol Oncol. 1999; 73: 247-252
        • Dietmaier W.
        • Wallinger S.
        • Bocker T.
        • et al.
        Diagnostic microsatellite instability: Definition and correlation with mismatch repair protein expression.
        Cancer Res. 1997; 57: 4749-4756
        • Boland C.R.
        • Thibodeau S.N.
        • Hamilton S.R.
        • et al.
        A National Cancer Institute Workshop on microsatellite instability for cancer detection and familial predisposition: Development of international criteria for the determination of microsatellite instability in colorectal cancer.
        Cancer Res. 1998; 58: 5248-5257
        • Thibodeau S.N.
        • Bren G.
        • Schaid D.
        • et al.
        Microsatellite instability in cancer of the proximal colon.
        Science. 1993; 260: 816-819
        • Zhou X-P
        • Hoang J-M
        • Li Y-J
        • et al.
        Determination of the replication error phenotype in human tumors without the requirement for matching normal DNA by analysis of mononucleotide repeat microsatellites.
        Genes Chrom Cancer. 1998; 21: 101-107
        • Renault B.
        • Calistri D.
        • Buonsanti G.
        • et al.
        Microsatellite instability and mutations of p53 and TGF-β RII genes in gastric cancer.
        Hum Genet. 1996; 98: 601-607
        • Olschwang S.
        • Hamelin R.
        • Laurent-Puig P.
        • et al.
        Alternative genetic pathways in colorectal carcinogenesis.
        Proc Natl Acad Sci. 1997; 94: 12122-12127
        • Oliveira C.
        • Seruca R.
        • Seixas M.
        • et al.
        The clinicopathological features of gastric carcinomas with microsatellite instability may be mediated by mutations of different ‘target genes’.
        Am J Pathol. 1998; 153: 1211-1219
        • Fujiwara T.
        • Stolker J.M.
        • Watanabe T.
        • et al.
        Accumulated clonal genetic alterations in familial sporadic colorectal carcinomas with widespread instability in microsatellite sequences.
        Am J Pathol. 1998; 153: 1063-1078
        • Tsujimoto Y.
        • Yunis Y.
        • Nowell P.C.
        • et al.
        Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation.
        Science. 1984; 226: 1097-1099
        • Williams M.E.
        • Meeker T.C.
        • Swerdlow S.H.
        Rearrangement of the chromosome 11 bcl-1 locus in centrocytic lymphoma: Analysis with multiple breakpoint probes.
        Blood. 1991; 78: 493-498
        • Ye B.H.
        • Rao P.H.
        • Chaganti R.S.K.
        • et al.
        Cloning of bcl-6, the locus involved in chromosome translocations affecting band 3q27 in B-cell lymphoma.
        Cancer Res. 1993; 53: 2732-2735