Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1995 Dec;86(12):1127–1130. doi: 10.1111/j.1349-7006.1995.tb03304.x

A Novel Somatic Point Mutation of the RET Proto‐oncogene in Tumor Tissues of Small Cell Lung Cancer Patients

Hitoyasu Futami 1,✉, Shin‐ichi Egawa 1, Toshihiko Tsukada 1, Kouji Maruyama 1, Shuji Bandoh 1, Masayuki Noguchi 2, Ken Yamaguchi 1
PMCID: PMC5920673  PMID: 8635999

Abstract

We examined whether the novel point mutation from GCC (Ala) to GAC (Asp) at codon 664 in exon 11 of RET proto‐oncogene, which we had found in two small cell lung carcinoma (SCLC) cell lines, existed in genomic DNA of tumor tissues of the two SCLC patients from whom these SCLC cell lines were derived. Sequence analysis revealed that point mutation identical to that of the SCLC cell lines was present in amplified alleles of single‐strand conformational variants in genomic DNA of the tumor tissues, whereas it was not detected in genomic DNA of non‐tumor tissues of the patients. These results indicate that this mutation had initially occurred in the SCLC patients and was of somatic origin.

Keywords: Small cell lung carcinoma, RET, Point mutation, Multiple endocrine neoplasia, Medullary thyroid carcinoma

Full Text

The Full Text of this article is available as a PDF (463.0 KB).

REFERENCES

  • 1. ) Takahashi , M. , Buma , Y. , Iwamoto , T. , Inaguma , Y. , Ikeda , H. and Hiai , H.Cloning and expression of the ret proto‐oncogene encoding a tyrosine kinase with two potential transmembrane domains . Oncogene , 3 , 571 – 578 ( 1988. ). [PubMed] [Google Scholar]
  • 2. ) Tahira , T. , Ishizaka , Y. , Itoh , F. , Sugimura , T. and Nagao , M.Characterization of ret proto‐oncogene mRNAs encoding two isoforms of the protein product in a human neuroblastoma cell line . Oncogene , 5 , 97 – 102 ( 1990. ). [PubMed] [Google Scholar]
  • 3. ) Ishizaka , Y. , Itoh , F. , Tahira , T. , Ikeda , I. , Ogura , T. , Sugimura , T. and Nagao , M.Presence of aberrant transcripts of ret proto‐oncogene in a human papillary thyroid carcinoma cell line . Jpn. J. Cancer Res. , 80 , 1149 – 1152 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. ) Grieco , M. , Santoro , M. , Berlingieri , M. T. , Melillo , R. M. , Donghi , R. , Bongarzone , I. , Pierotti , M. A. , Delia , P. G. , Fusco , A. and Vecchio , G.PTC is a novel rearranged form of the ret proto‐oncogene and is frequently detected in vivo in human thyroid papillary carcinomas . Cell , 60 , 557 – 563 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Bongarzone , I. , Monzini , N. , Borrello , M. G. , Carcano , C. , Ferraresi , G. , Arighi , E. , Mondellini , P. , Delia , P. G. and Pierotti , M. A.Molecular characterization of a thyroid tumor‐specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP‐dependent protein kinase A . Mol. Cell Biol , 13 , 358 – 366 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. ) Nagao , M. , Ishizaka , Y. , Nakagawara , A. , Kohno , K. , Kuwano , M. , Tahira , T. , Itoh , F. , Ikeda , I. and Sugimura , T.Expression of ret proto‐oncogene in human neuro‐blastomas . Jpn. J. Cancer Res. , 81 , 309 – 312 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Ikeda , I. , Ishizaka , Y. , Tahira , T. , Suzuki , T. , Onda , M. , Sugimura , T. and Nagao , M.Specific expression of the ret proto‐oncogene in human neuroblastoma cell lines . Oncogene , 5 , 1291 – 1296 ( 1990. ). [PubMed] [Google Scholar]
  • 8. ) Donis‐Keller , H. , Dow , S. , Chi , D. , Carlson , K. M. , Toshima , K. , Lairmore , T. C. , Howe , J. R. , Moley , J. F. , Goodfellow , P. and Wells , S. A.Mutations in the RET proto‐oncogene are associated with MEN 2A and FMTC . Hum. Mol. Genet. , 2 , 851 – 856 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Mulligan , L. M. , Kwok , J. B. J. , Healey , C. S. , Elsdon , M. J. , Eng , C. , Gardner , E. , Love , D. R. , Mole , S. E. , Moore , J. K. , Papi , L. , Ponder , M. A. , Teleniusf , H. , Tunnacliffe , A. and Ponder , B. A. J.Germ‐line mutations of the RET proto‐oncogene in multiple endocrine neo‐plasia type 2A . Nature , 363 , 458 – 460 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Hofstra , R. M. W. , Landsvater , R. M. , Caccherini , I. , Stulp , R. P. , Stelwagen , T. , Luo , Y. , Pasini , B. , Hoppener , J. W. M. , van Amstel , H. K. P. , Romeo , G. , Lips , C. J. M. and Buys , C. H. C. M.A mutation in the RET proto‐oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma . Nature , 367 , 375 – 376 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Edery , P. , Lyonnet , S. , Mulligan , L. M. , Pelet , A. , Dow , E. , Abel , L. , Holder , S. , Nihoul , F. C. , Ponder , B. A. and Munnich , A.Mutations of the RET proto‐oncogene in Hirschsprung's disease . Nature , 367 , 378 – 380 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Romeo , G. , Ronchetto , P. , Luo , Y. , Barone , V. , Seri , M. , Ceccherini , L , Pasini , B. , Bocciardi , R. , Lerone , M. , Kaariainen , H. and Martucciello , G.Point mutations affecting the tyrosine kinase domain of the RET proto‐oncogene in Hirschsprung's disease . Nature , 367 , 377 – 378 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Eng , C , Smith , D. P. , Mulligan , L. M. , Nagai , M. A. , Healey , C. S. , Ponder , M. A. , Gardner , E. , Scheumann , G. F. W. , Jackson , C. E. , Tunnacliffe , A. and Ponder , B. A. J.Point mutation within the tyrosine kinase domain of the RET proto‐oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours . Hum. Mol. Genet. , 3 , 237 – 241 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Yamaguchi , K. , Abe , K. , Adachi , I. , Suzuki , M. , Kimura , S. , Kameya , T. and Yanaihara , N.Concomitant production of immunoreactive gastrin‐releasing peptide and calcitonin in medullary carcinoma of the thyroid . Metabolism , 33 , 724 – 727 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Yamaguchi , K. , Abe , K. , Adachi , I. , Otsubo , K. , Nagasaki , K. , Suzuki , M. , Maruno , K. , Asanuma , F. , Tsuchihashi , T. , Miyake , Y. , Yoshinaga , K. , Matsubara , H. , Imanishi , K. , Kimura , S. , Kodama , T. , Kameya , T. and Shimosato , Y.Peptide hormone production in small cell lung carcinomas with particular reference to gastrin‐releasing peptide . Jpn. J. Clin. Oncol. , 16 , 235 – 241 ( 1986. ). [PubMed] [Google Scholar]
  • 16. ) Futami , H. , Egawa , S. and Yamaguchi , K.A novel point mutation of the RET proto‐oncogene in small cell lung carcinoma cell lines . Proc. Jpn. Acad. , 70B , 210 – 214 ( 1994. ). [Google Scholar]
  • 17. ) Yamaguchi , K. , Abe , K. , Kameya , T. , Adachi , I. , Taguchi , S. , Otsubo , K. and Yanaihara , N.Production and molecular size heterogeneity of immunoreactive gastrin‐releasing peptide in fetal and adult lungs and primary lung tumors . Cancer Res. , 43 , 3932 – 3939 ( 1983. ). [PubMed] [Google Scholar]
  • 18. ) Yamaguchi , K. , Abe , K. , Suzuki , M. , Adachi , I. , Kimura , S. , Shimada , A. , Ohno , H. , Kanai , A. and Kameya , T.Production of immunoreactive pancreatic growth hormone‐releasing factor in small cell carcinoma of the lung . Jpn. J. Cancer Res. , 74 , 814 – 817 ( 1989. ). [PubMed] [Google Scholar]
  • 19. ) Noguchi , M. , Maezawa , N. , Nakanishi , Y. , Matsuno , Y. , Shimosato , Y. and Hirohashi , S.Application of the p53 gene mutation pattern for differential diagnosis of primary versus metastatic lung carcinoma . Diagn. Mol. Pathol. , 2 , 29 – 35 ( 1993. ). [PubMed] [Google Scholar]
  • 20. ) Orita , M. , Suzuki , Y. , Sekiya , T. and Hayashi , K.Rapid and sensitive detection of point mutations and DNA polymorphism using the polymerase chain reaction . Genomics , 5 , 874 – 879 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Suzuki , Y. , Sekiya , T. and Hayashi , K.Allele‐specific polymerase chain reaction: a method for amplification and sequence determination of a single component among a mixture of sequence variants . Anal. Biochem. , 192 , 82 – 84 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Terasaki , T. , Kameya , T. , Nakajima , T. , Tsumuraya , M. , Shimosato , Y. , Kato , K. , Ichinose , H. , Nagatsu , T. and Hasegawa , T.Interconversion of biological characteristics of small cell lung cancer depending on culture conditions . Gann , 75 , 1089 – 1099 ( 1984. ). [PubMed] [Google Scholar]
  • 23. ) Santoro , M. , Carlomagno , F. , Romano , A. , Bottaro , D. P. , Dathan , N. A. , Grieco , M. , Fusco , A. , Vecchio , G. , Matoskova , B. , Kraus , M. H. and Fiore , P. P. D.Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B . Science , 267 , 381 – 383 ( 1995. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES