Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC)

Elaine H. Lim, Shen Li Zhang, Jia Liang Li, Wee See Yap, Tse Chiang Howe, Bien Peng Tan, Yong Shyan Lee, Daniel Wong, Kay Leong Khoo, Kar Yin Seto, Lenny Tan, Thirugananam Agasthian, Heng Nung Koong, John Tam, Christie Tan, Michael Caleb, Alex Y Chang, Alan Ng, Patrick Tan

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalJournal of Thoracic Oncology
Volume4
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Genome
Biopsy
Mutation
Lung
Survival
Mutation Rate
Parvovirus
Epithelial-Mesenchymal Transition
DNA
Sarcoma
Genes
Neoplasms

Keywords

  • Advanced stage
  • CMET mutations
  • Early stage
  • EGFR mutations
  • KRAS mutations
  • Low-volume biopsies
  • Non-small cell lung cancer
  • P53 mutations
  • Prognosis
  • Whole genome amplification

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC). / Lim, Elaine H.; Zhang, Shen Li; Li, Jia Liang; Yap, Wee See; Howe, Tse Chiang; Tan, Bien Peng; Lee, Yong Shyan; Wong, Daniel; Khoo, Kay Leong; Seto, Kar Yin; Tan, Lenny; Agasthian, Thirugananam; Koong, Heng Nung; Tam, John; Tan, Christie; Caleb, Michael; Chang, Alex Y; Ng, Alan; Tan, Patrick.

In: Journal of Thoracic Oncology, Vol. 4, No. 1, 01.2009, p. 12-21.

Research output: Contribution to journalArticle

Lim, EH, Zhang, SL, Li, JL, Yap, WS, Howe, TC, Tan, BP, Lee, YS, Wong, D, Khoo, KL, Seto, KY, Tan, L, Agasthian, T, Koong, HN, Tam, J, Tan, C, Caleb, M, Chang, AY, Ng, A & Tan, P 2009, 'Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC)', Journal of Thoracic Oncology, vol. 4, no. 1, pp. 12-21. https://doi.org/10.1097/JTO.0b013e3181913e28
Lim, Elaine H. ; Zhang, Shen Li ; Li, Jia Liang ; Yap, Wee See ; Howe, Tse Chiang ; Tan, Bien Peng ; Lee, Yong Shyan ; Wong, Daniel ; Khoo, Kay Leong ; Seto, Kar Yin ; Tan, Lenny ; Agasthian, Thirugananam ; Koong, Heng Nung ; Tam, John ; Tan, Christie ; Caleb, Michael ; Chang, Alex Y ; Ng, Alan ; Tan, Patrick. / Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC). In: Journal of Thoracic Oncology. 2009 ; Vol. 4, No. 1. pp. 12-21.
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abstract = "BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20{\%} versus 24{\%} (p = 0.48), 29{\%} versus 27{\%} (p = 0.75), 10{\%} versus 6{\%} (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.",
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T1 - Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC)

AU - Lim, Elaine H.

AU - Zhang, Shen Li

AU - Li, Jia Liang

AU - Yap, Wee See

AU - Howe, Tse Chiang

AU - Tan, Bien Peng

AU - Lee, Yong Shyan

AU - Wong, Daniel

AU - Khoo, Kay Leong

AU - Seto, Kar Yin

AU - Tan, Lenny

AU - Agasthian, Thirugananam

AU - Koong, Heng Nung

AU - Tam, John

AU - Tan, Christie

AU - Caleb, Michael

AU - Chang, Alex Y

AU - Ng, Alan

AU - Tan, Patrick

PY - 2009/1

Y1 - 2009/1

N2 - BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.

AB - BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.

KW - Advanced stage

KW - CMET mutations

KW - Early stage

KW - EGFR mutations

KW - KRAS mutations

KW - Low-volume biopsies

KW - Non-small cell lung cancer

KW - P53 mutations

KW - Prognosis

KW - Whole genome amplification

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