A rare case of squamous cell carcinoma of the lung harbouring ALK and BRAF activating mutations

Alrifai, Doraid; Popat, Sanjay; Ahmed, Merina; González, David; Nicholson, Andrew G.; Parcq, John du; Benepal, T.

doi:10.1016/j.lungcan.2013.02.002

Cited by 19 publications

(21 citation statements)

References 9 publications

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“…This is in contrast to the predominant findings in NSCLC, which show that concurrent ‘driver’ mutations such as EGFR mutation and ALK rearrangements may occur but are uncommon (36-39). This result is of particular clinical relevance as attempts to identify CRC cases harboring these fusion events cannot benefit from an enrichment strategy where patients with KRAS or BRAF mutations are excluded from further testing.…”

Section: Discussioncontrasting

confidence: 88%

ROS1 and ALK Fusions in Colorectal Cancer, with Evidence of Intratumoral Heterogeneity for Molecular Drivers

Aisner

Nguyen

Paskulin

et al. 2014

Molecular Cancer Research

106

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Activated ALK and ROS1 tyrosine kinases, through gene fusions, has been found in lung adenocarcinomas and are highly sensitive to selective kinase inhibitors. This study aimed at identifying the presence of these rearrangements in human colorectal adenocarcinoma (CRC) specimens using a 4-target, 4-color break-apart fluorescence in situ hybridization (FISH) assay to simultaneously determine the genomic status of ALK and ROS1. Among the clinical CRC specimens analyzed, rearrangement-positive cases for both ALK and ROS1 were observed. The fusion partner for ALK was identified as EML4 and the fusion partner for one of the ROS1-positive cases was SLC34A2, the partner for the other ROS1-positive case remains to be identified. A small fraction of specimens presented duplicated or clustered copies of native ALK and ROS1. In addition, rearrangements were detected in samples that also harbored KRAS and BRAF mutations in two of the three cases. Interestingly, the ALK-positive specimen displayed marked intra-tumoral heterogeneity and rearrangement was also identified in regions of high-grade dysplasia. Despite the additional oncogenic events and tumor heterogeneity observed, elucidation of the first cases of ROS1 rearrangements and confirmation of ALK rearrangements support further evaluation of these genomic fusions as potential therapeutic targets in CRC. Implications ROS1 and ALK fusions occur in colorectal cancer and may have substantial impact in therapy selection.

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Section: Discussioncontrasting

confidence: 88%

ROS1 and ALK Fusions in Colorectal Cancer, with Evidence of Intratumoral Heterogeneity for Molecular Drivers

Aisner

Nguyen

Paskulin

et al. 2014

Molecular Cancer Research

106

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“…The data are also supported by other studies specifically reporting the frequency of 0% ALK translocation in SCC patients [23][24][25]. Since the current practice guidelines recommend a molecular testing for lung adenocarcinoma or mixed lung cancer with an ADC component to select patients for targeted TKI therapy, reported cases of lung squamous cancer harboring gene rearrangements challenge the molecular diagnosis based on histologic subtypes [12,15,[26][27][28][29][30]. However, doubts have been cast on reports showing ALK and/or ROS1 rearrangements in squamous lung cancer, as the small biopsy specimens were not representative of the whole tumor characteristics, and an immunohistochemistry panel was not available to validate the squamous differentiation.…”

Section: Introductionsupporting

confidence: 69%

“…Based on these clinicopathologic characteristics, current recommendations for ALK molecular testing should be used to select patients for ALK-targeted TKI therapy within advanced, non-squamous NSCLC. However, tumors with squamous cell carcinoma or adenosquamous histologies, albeit at a lower frequency (∼1%) than adenocarcinomas, have been reported to carry ALK translocations [6,26,28,32,35,[40][41][42][43]. Based on the NanoString fusion panel, we have examined a total of 282 cases of lung SCC combining the 214 from this study and the 68 from the published results of Fang et al [32].…”

Section: Discussionmentioning

confidence: 99%

ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare

et al. 2016

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“…The co-occurrence of BRAF mutations with PIK3CA mutations, EGFR mutations, KRAS mutations and ALK translocations has previously been described in lung cancers, including two patients in the series by Marchetti et al . with concurrent BRAF V600E mutations and EGFR mutations and, in the series by Cadarella et al , one patient with a BRAF V600E mutation and a PIK3CA mutation and two patients with BRAF G464 mutations and KRAS mutations[11, 12, 27-29]. This underscores the role of multiplexed genotyping as more than one actionable oncogenic driver may exist within the same patient.…”

Section: Discussionmentioning

confidence: 96%

Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium

Villaruz

Socinski

Abberbock

et al. 2014

Cancer

109

105

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(1) PURPOSE The advent of effective targeted therapy in BRAFV600E mutant lung adenocarcinomas necessitates further exploration of the unique clinical features and behavior of advanced stage BRAF mutant lung adenocarcinomas. (2) PATIENTS AND METHODS We reviewed data from patients with advanced lung adenocarcinomas enrolled in the Lung Cancer Mutation Consortium whose tumors underwent testing for mutations in EGFR, KRAS, HER2, AKT1, BRAF, MEK1, NRAS, PIK3CA, ALK translocations, and MET amplification. (3) RESULTS Twenty-one BRAF mutations were identified in 951 patients with adenocarcinomas (2.2%: 95% CI 1.4 to 3.4%); 17 (81%: 95% CI 60 to 92%) were BRAFV600E and 4 were non-BRAFV600E mutations. Among the 733 cases tested for all 10 genes, BRAF mutations were more likely to occur in current or former smokers than most other genotypic abnormalities (BRAF versus sensitizing EGFR: 82% versus 36%, mid-P<0.001; versus ALK: 39%, mid-P=0.003; versus other mutations: 49%, mid-P=0.02; versus patients with more than one oncogenic driver (doubleton): 46%, mid-P=0.04.) The double mutation rate among patients with BRAF mutations was 16%, compared with 5% in patients with other genomic abnormalities (mid-P=0.045). Differences were not found in survival between patients with BRAF mutations and those with other genomic abnormalities (P>0.20). (4) CONCLUSIONS We demonstrate BRAF mutations occur in 2.2% of advanced stage lung adenocarcinomas, were most commonly V600E, were associated with distinct clinicopathologic features compared with other genomic subtypes and a high mutation rate in more than one gene, underscoring the importance of comprehensive genomic profiling in assessing patients with advanced lung adenocarcinomas.

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A rare case of squamous cell carcinoma of the lung harbouring ALK and BRAF activating mutations

Cited by 19 publications

References 9 publications

ROS1 and ALK Fusions in Colorectal Cancer, with Evidence of Intratumoral Heterogeneity for Molecular Drivers

ROS1 and ALK Fusions in Colorectal Cancer, with Evidence of Intratumoral Heterogeneity for Molecular Drivers

ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare

Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium

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