Increased Expression of N-myc in Human Small Cell Lung Cancer Biopsies Predicts Lack of Response to Chemotherapy and Poor Prognosis

Abstract

Amplified and increased expression of the myc family of protooncogenes (c- and N-myc) has been described to be associated with rapid proliferation in a number of cell lines, including small cell lung cancer (SCLC). In SCLC, c-myc was demonstrated to be amplified in a subset of SCLC cell lines denoted as variant type, which show a more aggressive way of growth in vitro. The N-myc oncogene, which has extensive homology in the second exon with c-myc, has been shown to be implicated in the oncogenesis of several primary tumors, including SCLC. The authors describe, using in situ hybridization, that increased expression of the N-myc oncogenes in primary biopsies from 15 untreated patients with SCLC are strongly associated with poor response to chemotherapy, rapid tumor growth, and short survival.

MYC oncogenes and human neoplastic disease

“…In addition to the infrequent L-MYC ampli®cation in SCLC discussed above, both C-MYC and N-MYC ampli®cation and overexpression have also been observed (Little et al, 1983;Saksela et al, 1984;Nau et al, 1986;Funa et al, 1987;Johnson et al, 1987Johnson et al, , 1992Gu et al, 1988;Takahashi et al, 1989;Noguchi et al, 1990;Makela et al, 1992;Rygaard et al, 1993). The frequency of ampli®cation/overexpression for either gene has generally ranged from 2 ± 30% of all tumors, xenografts or cell lines and the extent of ampli®cation has ranged from 5 ± 4100-fold.…”

The N-myc Oncogene: Maximizing its Targets, Regulation, and Therapeutic Potential

“…DNA amplification of N-myc occurs in a subset of rhabdomyosarcoma, a pediatric soft-tissue sarcoma, and is predominantly found in the alveolar subset and rarely in the more common embryonal subtype (30), although N-myc mRNA and protein expression is found in the vast majority of all rhabdomyosarcoma cases regardless of histology (31). N-myc is amplified in 15% to 20% of small-cell lung cancers (32,33) and is associated with poor response to chemotherapy, rapid tumor growth, and shorter survival (34). N-myc amplification rarely occurs in other lung cancer histologies.…”

IN Situ Hybridization for Detection OF Hormone and Peptide mRNA in Carcinoid Tumors

“…Initially 661 bp PstI fragment of bovine 0-PPT cDNA (15) containing the sequence from exon 3 to 6 was subcloned into transcription vector Riboprobe Gemini (Promega). RNA probe was transcribed by using SP 6 RNA polymerase and '3-UTP as previously described (17). ISH on carcinoid tumor tissue was performed as previously described ( 17) using the probe with high specific activity at 5-9 x lo8 cpm/pg.…”

“…RNA probe was transcribed by using SP 6 RNA polymerase and '3-UTP as previously described (17). ISH on carcinoid tumor tissue was performed as previously described ( 17) using the probe with high specific activity at 5-9 x lo8 cpm/pg. Strong hybridization signals on the tumor cells was obtained with lo6 cpm/section (Fig.…”