3p13

12CC4,HSPC215,MFH,QRF1,hFKH1B

t(3;9)(p14;p13) --> PAX5-FOXP1 in childhood ALL

B-progenitor ALL (single case)

Unknown

Contains the NH2 terminus of PAX5 with the DNA-binding paired, octapeptide and homeodomain-like domains and the COOH-terminus of FOXP1 containing its DNA-binding (Zn and FH) and transcriptional regulatory domains.

The fusion protein is predicted to retain the ability to bind to PAX5 and FOXP1 transcriptional targets, but no longer provide normal transcriptional regulatory functions of both genes.

t(3;14)(p14;q32)/B-cell malignancies IGH-FOXP1

t(3;14)(p14;q32) resulting in upregulated expression of FOXP1, is a rare aberration in B-NHL. The translocation occurs recurrently in MALT-type of marginal zone B-cell lymphomas (MZBCL) and diffuse large B cell lymphoma (DLBCL). Single cases with variant FOXP1 translocations involving unknown non-IG loci have been reported.
Of note, a significant number of DLBCL (with a predominantly ABC-like phenotype) and extranodal MZBCL displayed a strong expression of FOXP1 which is independent of genomic rearrangements of the FOXP1 locus. FOXP1-positivity was also found in numerous cases of cutaneous B-cell lymphomas and follicular lymphomas.

High expression of FOXP1 in DLBCL is associated with poor prognosis. Deregulation of FOXP1 in MALT lymphomas possibly leads to transformation to a more aggressive DLBCL.

t(3;14) was recorded as a sole aberration and as a part of complex karyotypes. In MALT lymphomas, translocations involving FOXP1, MALT1 and BCL10 are mutually exclusive.

No hybrid gene; 5 FOXP1 juxtaposed with 3 IGH enhancer. Molecular characteristics of FOXP1 variant translocations are unknown.

The occurrence of activated FOXP1 translocations in lymphoma indicates that FOXP1 functions as an oncogene. So far, mechanisms and molecular consequences of aberrant expression of FOXP1 in lymphomas not harboring 3p14/FOXP1 rearrangements are unknown. The preliminary data suggest that not the full-length protein, but smaller FOXP1 isoforms are atypically highly expressed in ABC-DLBCL cell lines. Their role in the disease process is currently investigated.

Solid tumors

FOXP1 abnormalities (overexpression, mislocalization or loss of FOXP1) are observed in a wide variety of cancers, particularly of epithelial origin.
FOXP1 located in the 3p region frequently deleted in multiple types of cancers is one of a few potential tumor suppressor genes. Genomic loss of FOXP1 correlates with a decrease in FOXP1 mRNA and/or a decrease in FOXP1 protein levels in a significant number of analyzed lung cancers and head and neck cancers. In addition, an aberrant cytoplasmic localization of FOXP1 has been observed in a number of epithelial malignancies. Whether that aberrant localization may be a mechanism for inactivation of FOXP1 remains to be determined. So far, the direct evidence that FOXP1 functions as a tumor suppressor gene is limited.
In contrast, increased nuclear expression of FOXP1 has been detected in renal cell carcinoma, some prostate cancers, endometrial cancers and breast cancers. The mechanisms leading to altered expression of FOXP1 in cancer are elusive.