DCC tumor suppressor gene is inactivated in hematologic malignancies showing monosomy 18

Abstract

DCC (deleted in colorectal cancer) is a candidate tumor suppressor gene recently identified on chromosome band 18q21. Loss of one DCC allele or decreased DCC expression occurs in more than 70% of colorectal cancers, suggesting that DCC inactivation constitutes a critical event in the development of these tumors. Using polymerase chain reaction amplification of cDNA, we have studied DCC expression in bone marrow from 4 patients with leukemia (1 chronic myeloid leukemia-blastic crisis, case 1; 1 acute myeloid leukemia, case 2; 1 T-cell acute lymphoblastic leukemia [ALL], case 3; 1 B-cell ALL, case 4) showing loss of one DCC allele due to monosomy 18. We also studied DCC expression in multiple control samples, including normal lymphocytes, normal tonsillar tissue, and leukemias without 18q abnormalities. Four primer pairs consistently amplified the predicted DCC sequences from cDNA prepared from all control samples. However, in samples with monosomy 18, DCC transcripts were either not detected (case 1) or detected at a very low level (cases 2, 3, and 4). Southern analysis showed no structural rearrangement of the remaining DCC locus in all leukemia samples. Thus, loss of DCC expression was demonstrated in association with loss of one DCC allele in all cases tested. These results suggest that, as for colorectal tumors, the inactivation of DCC can have a role in the development of hematologic malignancies.

An Asian variant of intravascular large B‐cell lymphoma: clinical, pathological and cytogenetic approaches to diffuse large B‐cell lymphoma associated with haemophagocytic syndrome

“…The same abnormalities were found in three additional cases of the present series (8p21 in case nos 14 and 23; 19q13 in case nos 14 and 15). Gains or losses involving chromosome 18, which is known to be associated with inactivation of the DCC tumour‐suppressor gene (Porfiri et al , 1993; Hamaguchi et al , 1998), also appeared to be common in both of the present series (75%) and those reported by Shimazaki et al (1999) (71%).…”

Additional cytogenetic abnormalities in adults with Philadelphia chromosome‐positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia Group B

“… §§der(17)t(17;18) with similar but not identical break points has also been reported in two cases of AML (Porfiri et al , 1993; Fugazza et al , 1997), one case of NHL (Nordgren et al , 2000) and one case of CML (Sessarego & Ajmar, 1987), a very similar rearrangement, described as der(17;18)(q10;q10), has also been reported as a non‐random secondary aberration in Philadelphia chromosome‐positive CML (Ravandi et al , 2001) and in several cases of other types of haematological malignancy, including CLL, RARS and AML (Mitelman et al , 2003). …”

Coexpression of tissue factor and tissue factor pathway inhibitor by human monocytes purified by leukapheresis and elutriation.Response of nonadherent cells to lipopolysaccharide

“…Primers were chosen in two different exons by using a biomolecular sequence database 20 (Bisance, Paris, France) for TF and TFPI and according to Porfiri et al 21 for β‐actin. Primer sequences (Gibco) are as follows:…”