Primary Pulmonary MALT Lymphomas Show Frequent and Heterogenous Cytogenetic Abnormalities, Including a Previously Unreported MALT1-IGH Translocation

Reviewer: Tracy d'Entremont, MD
OncoLink
Ultima Vez Modificado: 8 de diciembre del 2002

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Presenter: Ellen D. Remstein
Presenter's Affiliation: Mayo Clinic; Rochester, MN
Type of Session: Scientific

Background

  • Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B-cell malignant lymphoma that arises in diverse extranodal sites.
  • t(11;18)(q21;q21), which fuses AP12 to MALT1 is specifically associated with MALT lymphoma and is it's most frequent structural chromosomal abnormality
  • aneuploidy, particularly trisomy 3,7,12,and 18 is also common in MALT lymphoma
  • t(11;18)and aneuploidy occur predominantly in mutually exclusive subsets of MALT lymphomas suggesting different pathogenetic pathways.
  • Most cytogenetic analyses of MALT lymphomas have been conducted on gastric tumors
  • The range of cytogenetic abnormalities in primary pulmonary MALT lymphoma is unknown.

Materials and Methods

  • Flourescence in situ hybridization (FISH) was performed on paraffin embedded tissue from 28 primary pulmonary MALT lymphomas.
  • FISH probes for AP12-MALT1 were 2 color probes that spanned both breakpoints, resulting in a dual fusion pattern in positive cases.
  • Centromeric probes for chromosomes 3,7,12,and 18 were applied in all cases.

Results

  • 7/28 (25%) of primary pulmonary MALT lymphomas demonstrated the AP12-MALT1 fusion protein in a median of 65% of cells.
  • Of those AP12-MALT1 positive tumors, aneuploidy was rare, with only 2 cases also demonstrating trisomy 3.
  • 11/28 (39%) of cases were aneuploid alone with:
    10 cases of trisomy 3
    0 cases of trisomy 7
    3 cases of trisomy 12
    6 cases of trisomy 18
  • 3/28 (11%) of cases were + for MALT1-IGH
    2 of these 3 cases also had trisomy 3 and 12
    the other case had trisomy 11

Author's Conclusions

  • Cytogenetic abnormalities are frequent amd more complex in primary pulmonary MALT lymphomas than in those reported from other locations.
  • Aneuploidy and t(11;18) are predominantly seen in mutually exclusive groups, supporting the hypothesis that they represent different pathogenetic pathways.
  • A new potential pathogenetic pathway in which MALT1 may be activated by the IGH promoter region (MALT1-IGH) has also been identified.

Clinical/Scientific Implications

    MALT lyphomas are a heterogenous group of tumors. Understanding the genetic abnormalities of these tumors is important in describing the malignant phenotype and may help to uncover new targeted therapies.

Oncolink's ASH Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.



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