Close correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human lung cancer to the lymph nodes and other organs.

Abstract

Close correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human lung cancer to the lymph nodes and other organs (cancer ABSTRACTRestriction length fragment polymorphism of the L-MYC gene was examined in DNAs from lung cancer tissues and normal tissues of 51 Japanese patients with lung cancer. In individual patients, no difference was seen between the restriction length fragments of the two alleles of L-MYC [6-kilobase (kb) and 10-kb fragments in EcoRI digests] in lung cancer tissues and normal tissues. But a striking correlation was found between the restriction length fragment polymorphism pattern of L-MYC and the extent of metastasis, particularly to the lymph nodes at the time of surgery: Patients with only the L band (10 kb) had few lymph node metastatic lesions, whereas patients with either the S band (6 kb) or the S and L bands almost always had lymph node metastatic lesion. A similar correlation was found between the presence of the S band and metastases to other organs. This correlation was particularly marked in cases of adenocarcinoma. These results indicate a clear genetic influence on metastases and a consequent poor prognosis for certain patients of lung cancer; L-MYC restriction length fragment polymorphism is thus shown to be a useful marker for predicting the metastatic potential of human lung cancer.

Restriction fragment length polymorphism of the L-myc gene in oral cancer patients

“…However, a close correlation with the stage of differentiation of the tumours and the L-myc RFLP was observed. In contrast Kakehi and Yoshida (1989), in renal cancers, and Kawashima et al (1988), in lung cancers, did not observe such an association with the grade of tumour cell differentiation. An interesting question is how the presence of the S allele of L-myc could be related to the stage of differentiation selectively in oral cancers.…”

“…RFLP studies of the L-myc gene have demonstrated a close association of the S (6.6 kb) fragment with metastatic potential in lung cancer (Kawashima et al, 1988), colon and stomach cancers (Kawashima et al, 1987), and renal cell carcinomas (Kakehi & Yoshida, 1989). These studies indicated that the L (10.0kb) fragment was an indicator of better prognosis in the cancers.…”

“…(Botstein et al, 1980). One of the purposes of RFLP studies in cancer has been to establish a specific association of a particular proto-oncogene RFLP, with increased incidence of certain types of cancer, suggesting genetic predisposition (Krontiris et al, 1985;Heighway et al, 1986;Liderau et al, 1985Liderau et al, , 1986Kawashima et al, 1988;Kakehi & Yoshida, 1989 (Liderau et al, 1985). On the other hand, in urothelial cancers (Ishikawa et al, 1988) and colon adenocarcinomas (Ceccherini-Nelli et al, 1987), prevalence of specific Ha-ras polymorphic variants was not observed.…”

“…However, our results showed that oral cancer patients with a genotype including an S fragment are more likely to develop a poor to moderately differentiated tumour or a larger tumour than patients without an S fragment. The three reports of L-myc RFLP mentioned earlier were in the Japanese population (Kawashima et al, 1988;Kakehi & Yoshida, 1989;Ikeda et al, 1988). An analysis of the genotype distribution and the allelic frequencies from their combined data indicates a similar L-myc haplotype and allelic distribution pattern to that seen in the Indian population.…”

MYC oncogenes and human neoplastic disease

“…Scattered reports have suggested that individuals bearing the`short' (S) allele either have an increased incidence of certain tumors and/or that such tumors manifest a more aggressive behavior. The associated neoplasms include soft-tissue sarcomas (Kato et al, 1990), oral cancers (Saranath et al, 1990), colorectal cancers (Young et al, 1994), nonHodgkin's lymphoma (Crossen et al, 1994), breast cancer (Champeme et al, 1992), and non-SCLC lung cancer (Kawashima et al, 1988). In contrast, at least one report has suggested that the`SS' genotype protects against hepatocellular cancer (Taylor et al, 1993).…”