Analysis of mismatch repair defects in the familial occurence of lymphoma and colorectal cancer Journal Article
| Authors: | Teruya-Feldstein, J.; Greene, J.; Cohen, L.; Popplewell, L.; Ellis, N. A.; Offit, K. |
| Article Title: | Analysis of mismatch repair defects in the familial occurence of lymphoma and colorectal cancer |
| Abstract: | Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant disorder featuring familial clustering of colorectal and/or endometrial cancer, and other malignancies. Except for a rare case report, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) have not been considered part of HNPCC. Recent murine models for HNPCC have shown an increased incidence of B- and T-cell lymphoma, as well as tumors of the gastrointestinal tract and other organ systems, involving defects in genes resulting in faulty mismatch repair (MMR) of DNA. These MMR genes include MLH1, MSH2, MSH3, MSH6, PMS1 and PMS2. We sought to analyze the occurrence of NHL and HD in families with clusters of colorectal cancers (CRC). Probands from 21 kindreds were classified as HNPCC (3), HNPCC-like (5), and HNPCC-variant (13); seen and followed by Clinical Genetics at Memorial Hospital the kindreds were assessed for the occurrence of NHL or HD. Of the 21 pedigrees, a total of 37 patients were identified who were diagnosed with leukemia, lymphoma, or HD. Fourteen of the 37 patients with a diagnosis of NHL or HD were further classified and showed varying histologies ranging from chronic lymphocytic leukemia/small lymphocytic lymphoma (2), mycosis fungoides (1), follicular lymphoma (1), extranodal marginal zone lymphoma of MALT type (2), diffuse large B-cell lymphoma (4), nodular sclerosis HD (3), and mixed cellularity HD (1). Microsatellite instability studies were performed on 6 cases but none showed evidence of replication error repair defects. Immunohistochemical stains performed on paraffin sections from these 6 representative cases showed differential protein expression of MLH1, MSH2, MSH6, and PMS2 when compared to normal reactive tissues from the same patient but showed no significant differences when compared to controls of non-familial, sporadic lymphomas. These results suggest that lymphomas arising in the setting of familial CRC do not bear the molecular hallmarks of HNPCC. Further studies are needed to explain the differential patterns of expression of RER-associated proteins in lymphomas, as well as the association of lymphomas and possibly renal cell cancers in a subset of kindreds in which CRC clustering is evident. |
| Keywords: | immunohistochemistry; adult; controlled study; human tissue; protein expression; aged; leukemia; carrier protein; dna binding protein; human cell; major clinical study; genetics; dna-binding proteins; histopathology; cancer diagnosis; cancer incidence; dna replication; colorectal cancer; disease association; familial disease; nuclear protein; neoplasm proteins; medical assessment; kidney carcinoma; hodgkin disease; nuclear proteins; b cell lymphoma; nonhodgkin lymphoma; dna; colorectal tumor; mismatch repair; microsatellite instability; carrier proteins; tumor protein; lymphoma; dna repair enzymes; genetic disorder; cancer classification; polydeoxyribonucleotide synthase; chronic lymphatic leukemia; adenosine triphosphatase; protein mlh1; mlh1 protein, human; lynch syndrome; protein msh2; protein msh6; colorectal neoplasms, hereditary nonpolyposis; pms2 protein, human; adenosine triphosphatases; follicular lymphoma; mycosis fungoides; autosomal dominant disorder; lymphocytoma; paraffin; pedigree analysis; statin; base mispairing; gastrointestinal tumor; base pair mismatch; mucosa associated lymphoid tissue lymphoma; hodgkin's disease; protein msh3; mismatch repair genes; humans; human; male; female; priority journal; article; support, non-u.s. gov't; hereditary non-polyposis colorectal cancer syndrome (hnpcc); adenosinetriphosphatase |
| Journal Title: | Leukemia and Lymphoma |
| Volume: | 43 |
| Issue: | 8 |
| ISSN: | 1042-8194 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2002-08-01 |
| Start Page: | 1619 |
| End Page: | 1626 |
| Language: | English |
| DOI: | 10.1080/1042819021000002956 |
| PUBMED: | 12400605 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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