Multiple Recurrent Genomic Defects in Follicular Lymphoma

Several steps in the clinical evolution of human neoplasia are associated with a variety of recurrent chromosomal defects that could prove essential to the understanding of cancer. We found 15 types of nonrandom chromosomal abnormalities in a study of 71 patients with follicular lymphoma; 10 of the types appeared to influence the histopathological findings, clinical course, or response to treatment. A translocation, t(14;18), observed in 85 percent of all patients appeared to be the main determinant of a follicular pattern. Ten patients with a t(14;18) as a single defect had the histologic features of follicular small cleaved-cell lymphoma. Most did not require treatment for one to four years, because their tumors had an initial indolent course. In contrast, patients with follicular small cleaved-cell lymphoma with t(14;18) and deletion 13q32 acquired the hematologic features of leukemia and had an acceleration of the disease. A deletion 6q together with a complete or partial trisomy 7 or trisomy 12 (or both) was associated with the clinically more aggressive follicular mixed small- and large-cell or large-cell histologic type, which often evolves from follicular small-cell lymphoma. A complete or partial trisomy 3, 18, or 21 correlated almost exclusively with follicular large-cell lymphoma. In all follicular stages, a trisomy 2 or duplication 2p often accompanied an accelerated clinical course and a poor response to treatment. This study suggests that several discrete genomic defects may govern the evolution of a patient's malignant disease. (N Engl J Med 1987; 316:79–84.), IT is becoming increasingly evident that most human leukemias and lymphomas are associated with characteristic chromosomal abnormalities.¹ They often involve either a reciprocal chromosome translocation, which may lead to oncogene deregulation, or a deletion of a chromosome band, which may represent a loss of a critical DNA sequence.¹ In malignant solid tumors and in non-Hodgkin's lymphomas, multiple chromosomal alterations have been observed and are thought to have a possible relation to tumor evolution, diversity, and clinical aggressiveness.² Except for a few nonrandom chromosomal abnormalities found at the terminal phase of chronic myelogenous leukemia,³ however, such genomic alterations have not been…