Array-CGH Identifies Regions, Including the FOXP1 Locus, Associated with Different Clinical Outcome in Diffuse Large B-Cell Lymphomas (DLBCL) Treated with R-CHOP

Background. Diffuse large B-cell lymphoma (DLBCL) consists of a heterogeneous group of tumors. More than 30% of cases are not cured with R-CHOP chemotherapy.

Aim. To identify genomic aberrations that could affect the response to therapy, we performed an arrayCGH study on uniformly treated DLBCL patients.

Materials and Methods. Tumor samples were analyzed with Affymetrix Human Mapping 250K SNP arrays. Eligibility criteria were diagnosis of de novo DLBCL, first line treatment with R-CHOP or R-CHOP-like regimens, availability of frozen biopsy and of clinical baseline and follow-up data. Exclusion criteria were: primary mediastinal DLBCL, primary central nervous system DLBCL, HIV-positivity. Material has been collected according to the local IRB guidelines. Results. Genomic tumor profiles have been obtained in 163 samples from 10 Institutions; 23/163 cases were excluded from this analysis because the information on response was not available; 140/163 cases fulfilled the study requirements. The clinical parameters of the patients reflected the normal DLBLC population, as shown by the IPI score distribution (0–1 in 30%, 2 in 37%, 3 in 23% and 4–5 in 10%). The median follow-up was 23 months (range 1–1251). Complete remission was observed in 108/140 (77%) patients, partial response in 21 (15%), stable disease in 6 (4%) and progression in 5 (2%). Genomic differences were observed between complete responders (108 cases) and the remaining patients, grouped together as poor responders (32 cases). The latter group had more gains of 3p14.1 (FOXP1 locus), 3q29, 11q24.3, and losses of 2p11.2-p13.3, 8p23.1- pter, 10p12.31-p13, 15q11.2-q14, 15q21.1 and copy neutral LOH of chromosome 9p. On the converse, 1q gains were more common among patients achieving complete remission. No differences were observed for other common region of gains (7, 12, 18q/BCL2) or losses (1p, 6q, 17p/TP53).

Conclusions. Specific genomic aberrations are associated with the response to R-CHOP in patients with DLBCL. In particular, the gain of the 3p14.1 (FOXP1 locus), which is associated with a lack of response to R-CHOP, suggests that the role of FOXP1 should be further investigated in DLBCL.