Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer

Louise Burke, Mohammed A. Khan, Andrew N. Freedman, Akihiko Gemma, Marek Rusin, Douglas G. Guinee, William P. Bennett, Ned E. Caporaso, Marian V. Fleming, William D. Travis, Thomas V. Colby, Victor Trastek, Peter C. Pairolero, Henry D. Tazelaar, David Eric Midthun, Lance A. Liotta, Curtis C. Harris

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Abstract

The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a candidate tumor suppressor gene linked to cancers of the lung, breast, colon, pancreas, and head and neck. Reports of frequent allelic deletion and abnormal transcripts in primary lung tumors pins recent evidence that it is targeted by tobacco smoke carcinogens suggest that it plays an important role in lung carcinogenesis. Non-small cell lung carcinoma still maintains a poor 5-year survival rate with the stage of disease at presentation as a major determinant of prognosis. We examined for allelic deletion at the FHIT locus in a series of 106 non-small cell lung carcinomas for which a full clinical, epidemiological, and 5-year survival profile was available. We found an allelic deletion frequency of 38% at one or two intragenic microsatellites. Allelic deletion of FHIT was related to tumor histology with 4 of 20 adenocarcinomas (20%) displaying loss of heterozygosity (LOH) compared with 12 of 22 (55%) nonadenocarcinomas (p = 0.03). We found that 63% of tumors with LOH of FHIT also had p53 missense mutations whereas only 26% with LOH had wild type p53 negative sequence (P = 0.02). We also found a significant trend toward poorer survival in patients with LOH of at least one locus of the FHIT gene (log rank, P = 0.01). This survival correlation is independent of tumor stage, size, histological subtype, degree of differentiation, and p53 mutation status. Our data support the hypothesis that the loss of the FHIT contributes to the molecular pathogenesis of human lung cancer and is an indicator of poor prognosis.

Original languageEnglish (US)
Pages (from-to)2533-2536
Number of pages4
JournalCancer Research
Volume58
Issue number12
StatePublished - Jun 15 1998

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Histidine
Non-Small Cell Lung Carcinoma
Loss of Heterozygosity
Survival
Genes
Lung Neoplasms
Neoplasms
Lung
Missense Mutation
Tumor Suppressor Genes
Smoke
Carcinogens
Microsatellite Repeats
Tobacco
Pancreas
Histology
Colon
Carcinogenesis
Adenocarcinoma
Neck

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Burke, L., Khan, M. A., Freedman, A. N., Gemma, A., Rusin, M., Guinee, D. G., ... Harris, C. C. (1998). Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer. Cancer Research, 58(12), 2533-2536.

Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer. / Burke, Louise; Khan, Mohammed A.; Freedman, Andrew N.; Gemma, Akihiko; Rusin, Marek; Guinee, Douglas G.; Bennett, William P.; Caporaso, Ned E.; Fleming, Marian V.; Travis, William D.; Colby, Thomas V.; Trastek, Victor; Pairolero, Peter C.; Tazelaar, Henry D.; Midthun, David Eric; Liotta, Lance A.; Harris, Curtis C.

In: Cancer Research, Vol. 58, No. 12, 15.06.1998, p. 2533-2536.

Research output: Contribution to journalArticle

Burke, L, Khan, MA, Freedman, AN, Gemma, A, Rusin, M, Guinee, DG, Bennett, WP, Caporaso, NE, Fleming, MV, Travis, WD, Colby, TV, Trastek, V, Pairolero, PC, Tazelaar, HD, Midthun, DE, Liotta, LA & Harris, CC 1998, 'Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer', Cancer Research, vol. 58, no. 12, pp. 2533-2536.
Burke L, Khan MA, Freedman AN, Gemma A, Rusin M, Guinee DG et al. Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer. Cancer Research. 1998 Jun 15;58(12):2533-2536.
Burke, Louise ; Khan, Mohammed A. ; Freedman, Andrew N. ; Gemma, Akihiko ; Rusin, Marek ; Guinee, Douglas G. ; Bennett, William P. ; Caporaso, Ned E. ; Fleming, Marian V. ; Travis, William D. ; Colby, Thomas V. ; Trastek, Victor ; Pairolero, Peter C. ; Tazelaar, Henry D. ; Midthun, David Eric ; Liotta, Lance A. ; Harris, Curtis C. / Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer. In: Cancer Research. 1998 ; Vol. 58, No. 12. pp. 2533-2536.
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abstract = "The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a candidate tumor suppressor gene linked to cancers of the lung, breast, colon, pancreas, and head and neck. Reports of frequent allelic deletion and abnormal transcripts in primary lung tumors pins recent evidence that it is targeted by tobacco smoke carcinogens suggest that it plays an important role in lung carcinogenesis. Non-small cell lung carcinoma still maintains a poor 5-year survival rate with the stage of disease at presentation as a major determinant of prognosis. We examined for allelic deletion at the FHIT locus in a series of 106 non-small cell lung carcinomas for which a full clinical, epidemiological, and 5-year survival profile was available. We found an allelic deletion frequency of 38{\%} at one or two intragenic microsatellites. Allelic deletion of FHIT was related to tumor histology with 4 of 20 adenocarcinomas (20{\%}) displaying loss of heterozygosity (LOH) compared with 12 of 22 (55{\%}) nonadenocarcinomas (p = 0.03). We found that 63{\%} of tumors with LOH of FHIT also had p53 missense mutations whereas only 26{\%} with LOH had wild type p53 negative sequence (P = 0.02). We also found a significant trend toward poorer survival in patients with LOH of at least one locus of the FHIT gene (log rank, P = 0.01). This survival correlation is independent of tumor stage, size, histological subtype, degree of differentiation, and p53 mutation status. Our data support the hypothesis that the loss of the FHIT contributes to the molecular pathogenesis of human lung cancer and is an indicator of poor prognosis.",
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AU - Khan, Mohammed A.

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AU - Rusin, Marek

AU - Guinee, Douglas G.

AU - Bennett, William P.

AU - Caporaso, Ned E.

AU - Fleming, Marian V.

AU - Travis, William D.

AU - Colby, Thomas V.

AU - Trastek, Victor

AU - Pairolero, Peter C.

AU - Tazelaar, Henry D.

AU - Midthun, David Eric

AU - Liotta, Lance A.

AU - Harris, Curtis C.

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N2 - The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a candidate tumor suppressor gene linked to cancers of the lung, breast, colon, pancreas, and head and neck. Reports of frequent allelic deletion and abnormal transcripts in primary lung tumors pins recent evidence that it is targeted by tobacco smoke carcinogens suggest that it plays an important role in lung carcinogenesis. Non-small cell lung carcinoma still maintains a poor 5-year survival rate with the stage of disease at presentation as a major determinant of prognosis. We examined for allelic deletion at the FHIT locus in a series of 106 non-small cell lung carcinomas for which a full clinical, epidemiological, and 5-year survival profile was available. We found an allelic deletion frequency of 38% at one or two intragenic microsatellites. Allelic deletion of FHIT was related to tumor histology with 4 of 20 adenocarcinomas (20%) displaying loss of heterozygosity (LOH) compared with 12 of 22 (55%) nonadenocarcinomas (p = 0.03). We found that 63% of tumors with LOH of FHIT also had p53 missense mutations whereas only 26% with LOH had wild type p53 negative sequence (P = 0.02). We also found a significant trend toward poorer survival in patients with LOH of at least one locus of the FHIT gene (log rank, P = 0.01). This survival correlation is independent of tumor stage, size, histological subtype, degree of differentiation, and p53 mutation status. Our data support the hypothesis that the loss of the FHIT contributes to the molecular pathogenesis of human lung cancer and is an indicator of poor prognosis.

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