Incidental detection of JAK2 V617F mutations in next-generation sequencing analysis of solid tumours: a guide to further workup

Objectives

Genomic alterations related to hematopoietic elements may be seen in solid tumour next-generation sequencing (NGS) panels. Here, we report the incidental finding of JAK2 V617F mutations in NGS performed on solid tumours.

Methods

Cases where JAK2 V617F mutation was detected on solid tumour NGS performed in-house between 2016 and 2021 were analysed.

Results

12 cases (0.2%) of solid tumour NGS testing that identified JAK2 V617F were reviewed. The mean age of the patient population was 73.8 years (range: 53–87 years). The diagnosis included lung carcinoma ((n=9); adenocarcinoma (n=7), non-small cell carcinoma of the lung (n=1), metastatic adenocarcinoma, favour lung primary (n=1)), renal cell carcinoma-unclassified (1), undifferentiated malignant neoplasm (1) and metastatic poorly differentiated CK7 positive carcinoma (1).

The variant allele frequency (VAF) for the JAK2 V617F mutation ranged from 2.4 to 18.4% (mean: 8.2%) and was consistently and statistically significantly different from the VAF observed for tumour-specific genomic variants based on Wilcoxon test. On further work-up, 8/12 patients had clinical history or laboratory evidence of an underlying clonal myeloid process, 6/12 patients had evidence of a JAK2 V617F positive myeloid neoplasm while 2/12 had evidence of pre-treatment thrombocytosis. The remaining two patients had no prior history of a myeloid neoplasm or documented abnormal blood counts.

Conclusion

A work-up for potential haematological disease should be undertaken when an alteration associated with haematological neoplasms is identified in solid tumour NGS panels, particularly when the VAF is different compared to the VAF of other tumour-associated variants.