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Somatic STK11 and concomitant STK11/KRAS mutational frequency in stage IV lung adenocarcinoma adrenal metastases
Ferga C Gleeson1, Benjamin R Kipp, Michael J Levy
1*Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; †Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; ‡Division of Biomedical Statics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; and §Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.
Abstract:
Somatic serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) is a tumor suppressor gene and ranks as the third most frequently mutated gene in lung adenocarcinoma. However, current molecular testing guidelines recommend evaluating for epidermal growth factor receptor mutations and ALK fusions to guide therapy in all patients with advanced stage adenocarcinoma, regardless of gender, race, or smoking history. Identifying alternative "driver" mutations and using actionable targeted pharmacotherapy is a key approach to providing effective individualized medical care. The analytical sensitivity and parallel multigene approach of targeted next-generation sequencing is an attractive methodology for use for cytology specimens. The presented lung adenocarcinoma study revealed that STK11 mutations alone and concomitant KRAS/STK11 mutations were identified in 18.2% and 4.5% of solitary adrenal metastases, respectively. Molecular profiling of epidermal growth factor receptor tyrosine kinase inhibitor resistant tumors may help to identify patients who would most benefit from alternative single or dual pathway inhibition potentially leading to a revision in current molecular testing guidelines.
Insights
STK11 mutations are common in lung adenocarcinoma, particularly with KRAS. Identifying these driver mutations can guide targeted therapies beyond current EGFR and ALK testing, improving personalized lung cancer treatment.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Somatic serine/threonine kinase 11 (STK11), also known as liver kinase B1 (LKB1), is a crucial tumor suppressor gene frequently mutated in lung adenocarcinoma.
- Current guidelines for advanced lung adenocarcinoma therapy focus on epidermal growth factor receptor (EGFR) mutations and ALK fusions, potentially overlooking other significant genetic alterations.
- Identifying alternative driver mutations is essential for advancing personalized medicine and targeted pharmacotherapy in lung cancer.
Purpose of the Study:
- To investigate the prevalence and clinical significance of STK11 mutations in lung adenocarcinoma, particularly in the context of adrenal metastases.
- To evaluate the utility of targeted next-generation sequencing (NGS) for detecting these mutations in cytology specimens.
- To explore the potential for revising current molecular testing guidelines based on findings of STK11 and concomitant KRAS/STK11 mutations.
Main Methods:
- Analysis of solitary adrenal metastases from lung adenocarcinoma patients using targeted next-generation sequencing.
- Assessment of STK11 mutations alone and in conjunction with KRAS mutations.
- Review of molecular profiling data from epidermal growth factor receptor tyrosine kinase inhibitor-resistant tumors.
Main Results:
- STK11 mutations were identified in 18.2% of solitary adrenal metastases.
- Concomitant KRAS/STK11 mutations were found in 4.5% of these metastases.
- Targeted NGS demonstrated analytical sensitivity for detecting these mutations in cytology samples.
Conclusions:
- STK11 mutations represent a significant, actionable subset of driver mutations in lung adenocarcinoma.
- Molecular profiling, including STK11 and KRAS analysis, can identify patients benefiting from alternative targeted therapies.
- These findings suggest a need to revise current molecular testing guidelines to incorporate STK11 mutation status for advanced lung adenocarcinoma.
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