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ALK Deletion Exons 2 to 19: Case Report of a Rare ALK Inhibitor-Responsive Lung Cancer Driver Oncogene
Zachary R Schoepflin1, Emmeline Academia1, Soravis A Osataphan1
1Department of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Abstract:
ALK internal deletions of nonkinase domain exons occur in 0.01% of lung cancers with ALK genomic aberrations. We report a lung adenocarcinoma with a previously undescribed somatic ALK deletion of exons 2 to 19 with dramatic and sustained (>23 mo) response to alectinib. Our and other reported cases with ALK nonkinase domain deletions (between introns and exons 1-19) can display positive results in nonsequencing-based lung cancer diagnostic tests (such as immunohistochemistry) used to screen for more common ALK rearrangements. This case report emphasizes that "ALK-driven" lung cancers should be expanded to encompass those harboring not only ALK rearrangements with other genes but also ALK nonkinase domain deletions.
Insights
A rare ALK nonkinase domain deletion in lung cancer responded dramatically to alectinib. This finding expands the definition of ALK-driven lung cancers beyond typical rearrangements.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Anaplastic Lymphoma Kinase (ALK) gene rearrangements are common drivers in lung adenocarcinoma.
- Internal deletions within the ALK nonkinase domain are rare genomic aberrations, occurring in approximately 0.01% of lung cancers with ALK alterations.
Observation:
- A case of lung adenocarcinoma presented with a novel somatic deletion of ALK exons 2 to 19.
- This specific deletion was previously undescribed in the literature.
Findings:
- The patient exhibited a dramatic and sustained response to alectinib, lasting over 23 months.
- ALK nonkinase domain deletions, similar to this case, can lead to false-positive results in non-sequencing based diagnostic tests like immunohistochemistry.
Implications:
- This case broadens the understanding of "ALK-driven" lung cancers to include nonkinase domain deletions.
- It highlights the importance of considering diverse ALK alterations in lung cancer diagnosis and treatment.
- Further research into the clinical significance and diagnostic approaches for these rare deletions is warranted.
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