Detection of single and associated lesions of the Bcl-1, Bcl-2, Bcl-6, c-myc, p53 and p16 genes in B-cell non-Hodgkin's lymphomas: value of molecular analysis for a better assignment of the histologic subtype.
OBJECTIVE
Molecular genetic abnormalities have been frequently described in non-Hodgkin's lymphomas (NHL). These lesions have been associated with specific entities, allowing a better categorization of NHL. However, these abnormalities are not as specific as initially described and their association is still unknown.


METHODS
By Southern blot and polymerase chain reaction, we have simultaneously analyzed the proto-oncogenes Bcl-1, Bcl-2, Bcl-6, c-myc and MLL and the tumor suppressor genes p53 and p16, in 100 unselected B-cell NHL patients at diagnosis, to establish its incidence throughout the different NHL subtypes, defined both by Working Formulation and REAL classifications, and to assess the frequency of co-existence of two or more genetic lesions within each individual patient.


RESULTS
Fifty two cases displayed some genetic abnormality. Bcl-1, altered in 12 cases, was highly specific to mantle cell lymphomas (57% of them), but 6 cases had a different histologic subtype. Bcl-2 was rearranged in 26 cases: 70% in follicular lymphomas (FL) and 20% in diffuse large cell lymphomas; these abnormalities were also present in other subtypes, i.e. marginal lymphomas (30%). Bcl-6 abnormalities were mostly found in diffuse large cell lymphomas (29%) but also found in other subgroups, like FL (14%). C-myc rearrangements were specific to Burkitt's lymphoma. MLL gene was always germline. Deletions and/or rearrangements of p53 and p16 genes were rare (4% and 8% of all cases, respectively). Finally, association of genetic lesions was a relatively common finding (13% of cases), especially in cases with adverse prognostic morphologies according to the REAL.


CONCLUSIONS
Molecular abnormalities are frequent in NHL at diagnosis, not only as unique lesions but also associated. A relative high specificity of some alterations was seen, thereby contributing to a better assessment of the histological subtype.
García-Sanz
R
R
Department of Hematology, Hospital Universitario De Salamanca, Spain.
Vargas Montero
M
M
Gonzalez Díaz
M
M
del Carmen
M
M
Santos
C
C
Balanzategui Echevarria
A
A
Flores Corral
T
T
Hernández Martín
J M
JM
Caballero Barrigón
M D
MD
San Miguel
J F
JF
D015139:Blotting, Southern; D017353:Gene Deletion; D015321:Gene Rearrangement / Q000235:genetics; D019940:Genes, bcl-1 / Q000235:genetics*; D019254:Genes, bcl-2 / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D019942:Genes, p16 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000145:classification* / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000145:classification* / Q000235:genetics*; D016133:Polymerase Chain Reaction