Open AccessMicrosatellite Instability and k‐ ras, p53 Mutations in Thyroid Lymphoma
Author(s) -
Takakuwa Tetsuya,
Hongyo Tadashi,
Syaifudin Mukh,
Kanno Hiroyuki,
Matsuzuka Fumio,
Narabayashi Isamu,
Nomura Taisei,
Aozasa Katsuyuki
Publication year - 2000
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2000.tb00942.x
Subject(s) - microsatellite instability , lymphoma , biology , pathology , cancer research , thyroid , thyroid lymphoma , mutation , microsatellite , immunology , medicine , thyroiditis , endocrinology , genetics , gene , allele
Patho‐epidemiological studies showed that thyroid lymphoma (TL) arises in inflammatory lesions of chronic lymphocytic thyroiditis (CLTH). Replication error (RER) is found in inflammatory lesions and associated cancer, suggesting that chronic inflammation could be a risk factor for neoplastic development through causing RER. To clarify whether RER is involved in the pathogenesis of TL, we examined the microsatellite instability (MSI) in 9 cases with CLTH and 19 with TL, including 10 diffuse large B‐cell lymphoma (DLBL), 4 follicle center cell lymphoma, 3 marginal zone B‐cell lymphoma of extranodal (MALT) type, and 2 lymphoplasmacytic type. Sixteen distinct microsatellite repeats were analyzed. Mutations of p53 and k‐ ras genes were also examined. When alterations at 2 or more microsatellite loci were judged as positive, only 5 DLBL cases exhibited MSI. The frequency of MSI in DLBL was significantly higher than that in other types of TL and CLTH ( P < 0.05). Four of 19 cases (21.1%) showed point mutation of the k‐ ras gene. The k‐ ras mutations occurred in the cases with DLBL with RER, and four of five cases with RER had a k‐ ras mutation, indicating a close association between RER and k‐ ras mutation. p53 mutations were not found in the CLTH. Two of 19 TL cases showed mutations of p53 gene. There was no significant association between RER and p53 mutation. These findings indicate that genomic instability contributes to the progression of TL from low grade to high grade, but not to the development of low grade lymphoma in CLTH lesions.