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Mutation patterns i...
Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11
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- La Fleur, Linnea (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Johan Botling
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- Falk-Sörqvist, Elin (author)
- Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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- Smeds, Patrik (author)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Berglund, Anders (author)
- EpiStat (Epidemiology & Statistics Consulting) Sweden
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- Sundström, Magnus (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Johan Botling
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- Mattsson, Johanna Sofia Margareta, 1985- (author)
- Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Brandén, Eva (author)
- Uppsala University,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Dept. of Respiratory Medicine, Gävle Hospital, Gävle
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- Koyi, Hirsh (author)
- Uppsala University,Karolinska Institutet,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Dept. of Respiratory Medicine, Gävle Hospital, Gävle
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- Isaksson, Johan (author)
- Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk och experimentell patologi,Centrum för klinisk forskning, Gävleborg,Dept. of Respiratory Medicine, Gävle Hospital, Gävle
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- Brunnström, Hans (author)
- Lund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups
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- Nilsson, Mats (author)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik
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- Micke, Patrick (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Patrick Micke
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- Moens, Lotte (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Johan Botling
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- Botling, Johan (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Johan Botling
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English.
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In: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 130, s. 50-58
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https://doi.org/10.1...
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Abstract
Subject headings
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- OBJECTIVES: Non-small cell lung cancer (NSCLC) is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients, as well as significant differences in populations across the world with regard to mutation spectra and mutation frequencies. Here we aim to describe mutational patterns and linked clinical parameters in a population-based NSCLC cohort.MATERIALS AND METHODS: Using targeted resequencing the mutational status of 82 genes was evaluated in a consecutive Swedish surgical NSCLC cohort, consisting of 352 patient samples from either fresh frozen or formalin fixed paraffin embedded (FFPE) tissues. The panel covers all exons of the 82 genes and utilizes reduced target fragment length and two-strand capture making it compatible with degraded FFPE samples.RESULTS: We obtained a uniform sequencing coverage and mutation load across the fresh frozen and FFPE samples by adaption of sequencing depth and bioinformatic pipeline, thereby avoiding a technical bias between these two sample types. At large, the mutation frequencies resembled the frequencies seen in other western populations, except for a high frequency of KRAS hotspot mutations (43%) in adenocarcinoma patients. Worse overall survival was observed for adenocarcinoma patients with a mutation in either TP53, STK11 or SMARCA4. In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration. Similar results were seen in the analysis of publicly available data from the cBioPortal. In squamous cell carcinoma a worse prognosis could be observed for patients with MLL2 mutations, while CSMD3 mutations were linked to a better prognosis.CONCLUSION: Here we have evaluated the mutational status of a NSCLC cohort. We could not confirm any survival impact of isolated driver mutations. Instead, concurrent mutations in TP53 and STK11 were shown to confer poor survival in the KRAS-positive adenocarcinoma subgroup.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- KRAS
- Mutation patterns
- Non-small cell lung cancer
- STK11
- TP53
- Targeted resequencing
- Patologi
- Pathology
- KRAS
- Mutation patterns
- Non-small cell lung cancer
- STK11
- Targeted resequencing
- TP53
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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La Fleur, Linnea
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Falk-Sörqvist, E ...
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Smeds, Patrik
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Berglund, Anders
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Sundström, Magnu ...
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Mattsson, Johann ...
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show more...
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Brandén, Eva
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Koyi, Hirsh
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Isaksson, Johan
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Brunnström, Hans
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Nilsson, Mats
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Micke, Patrick
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Moens, Lotte
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Botling, Johan
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Clinical Laborat ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Lung Cancer
- By the university
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Uppsala University
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Stockholm University
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Karolinska Institutet
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Lund University