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)…”

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%).…”

The dependence receptors DCC and UNC5H as a link between neuronal guidance and survival

“…The observation that DCC expression was lost/reduced in colorectal cancer suggested that DCC presence is a negative constraint for tumor development. Along this line, LOH of chromosome 18q and/or decreased DCC expression have also been detected in various other cancers, including gastric (Uchino et al, 1992) (Fang et al, 1998) (Yoshida et al, 1998), prostate (Brewster et al, 1994) (Latil et al, 1994) (Latil et al, 2003), endometrial (Imamura et al, 1992) (Gima et al, 1994) (Saegusa et al, 1999), ovarian (Enomoto et al, 1995) (Saegusa et al, 2000), esophageal (Huang et al, 1992) (Dolan et al, 1998), breast (Devilee et al, 1991) (Thompson et al, 1993), testicular (Murty et al, 1994) (Strohmeyer et al, 1997), glial (Scheck andCoons, 1993) (Reyes-Mugica et al, 1997), neuroblastoma (Kong et al, 1997) (Reyes-Mugica et al, 1998, and hematologic (Porfiri et al, 1993) (Miyake et al, 1993) (Miyake et al, 1994) malignancies. In most of studies, chromosome 18q LOH and loss of DCC expression have been associated with poor prognosis in colorectal cancer patients (Jen et al, 1994) (Lanza et al, 1998) (Sun et al, 1999) (Saito et al, 1999) (Saw et al, 2002) and with decreased responsiveness to chemotherapeutic agent like 5-fluorouracil-based adjuvant (Barratt et al, 2002).…”