Paquette R L, Berenson J, Lichtenstein A, McCormick F, Koeffler H P
Division of Hematology/Oncology, UCLA 90024.
Oncogene. 1990 Nov;5(11):1659-63.
Alterations of ras, c-myc and bcl-1 have been described in hematologic malignancies of lymphoid origin. We investigated the structure of these genes and evaluated the frequency of point mutations involving H-, K- or N-ras in bone marrow samples from patients with multiple myeloma. No abnormalities were detected in the c-myc and bcl-1 genes, but two of 17 patients were found to have N-ras mutations by differential oligonucleotide hybridization and dideoxynucleotide sequencing following amplification by polymerase chain reaction. Bone marrow DNA from both patients had identical missense mutations of N-ras codon 61 changing CAA to AAA, resulting in a substitution of lysine for glutamine in the encoded protein. Multiple myeloma is the first mature B cell neoplasm found to harbor ras mutations.
已在淋巴源性血液系统恶性肿瘤中描述了ras、c-myc和bcl-1的改变。我们研究了这些基因的结构，并评估了多发性骨髓瘤患者骨髓样本中涉及H-ras、K-ras或N-ras的点突变频率。在c-myc和bcl-1基因中未检测到异常，但通过聚合酶链反应扩增后进行的差异寡核苷酸杂交和双脱氧核苷酸测序发现，17例患者中有2例存在N-ras突变。两名患者的骨髓DNA均具有相同的N-ras密码子61错义突变，将CAA变为AAA，导致编码蛋白中的谷氨酰胺被赖氨酸取代。多发性骨髓瘤是首个被发现存在ras突变的成熟B细胞肿瘤。
