J Cancer 2018; 9(23):4341-4345. doi:10.7150/jca.27414 This issue

Research Paper

Detection of Exon 12 and 14 Mutations in Janus Kinase 2 Gene Including a Novel Mutant in V617F Negative Polycythemia Vera Patients from Pakistan

Afia Muhammad Akram1✉, Humera kausar2, Asma Chaudhary1, Ahmad Mukhtar Khalid3, Muhammad Mudassar Shahzad1, Muhammad Waheed Akhtar4, Muhammad Farooq Sabar5, Nadia Sajid6, Nawaf Al Anazi7, Aamer Aleem8, Zafar Iqbal7

1. Department of Zoology, Division of Science and technology, University of Education, Township, Lahore, Pakistan.
2. Department of biotechnology, Kinnaird College for Women, Lahore.
3. Department of Biotechnology, University of Sialkot, Sialkot, Pakistan.
4. School of biological sciences, University of The Punjab, Lahore, Pakistan.
5. Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, Pakistan.
6. Department of Hematology and Oncology, Institute of Nuclear Medicine and Oncology, lahore, Pakistan
7. Cancer and Medical Genetics, CAMS-A, King Saud Bin Abdulaziz University for Health Sciences & King Abdullah International Medical Research Centre (KAIMRC), King Abdulaziz Medical City, National Guard Health Affairs, Al Ahsa, Saudi Arabia.
8. KKUH, King Saud University, Riyadh, Saudi Arabia.

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Akram AM, kausar H, Chaudhary A, Khalid AM, Shahzad MM, Akhtar MW, Sabar MF, Sajid N, Anazi NA, Aleem A, Iqbal Z. Detection of Exon 12 and 14 Mutations in Janus Kinase 2 Gene Including a Novel Mutant in V617F Negative Polycythemia Vera Patients from Pakistan. J Cancer 2018; 9(23):4341-4345. doi:10.7150/jca.27414. Available from https://www.jcancer.org/v09p4341.htm

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The most frequently reported genetic aberration among polycythemia vera (PV) patients is a gain of function mutation V617F in exon 14 of Janus kinase 2 (JAK2) gene. However in many investigations, V617F negative PV patients have been reported to harbor mutations in JAK 2 exon 12. We investigated 24 patients with PV (diagnosed following 2016 WHO guidelines) to detect V617F mutation through allele specific PCR. The frequency of which was found to be 19/24 (79.2 %). Later on JAK2 exon 12 and 14 was amplified by conventional PCR in V617F negative patients and subjected to sequence analysis. A total of 03 mutated sites in exon 12 were detected in only two V617F-negative patients 2/5 (40%). All three substitutions were heterozygous i.e. F537F/I found in both patients and R528R/T, which is a novel mutation. In addition, one patient 1/5 (10%) manifested amino acid substitution V617A in JAK2 exon 14. Hematological parameters of individuals harboring mutations do not vary significantly than rest of the PV patients. Previous history and 2.3 years of follow-up studies reveal 15-year survival of V617F positive patients (n=19) to be 76%, while it is 94% for wild type V617 patients (n=05). Mean TLC of the patient cohort was 17.6± 9.1 x 109/L, mean platelet count was 552± 253 x 109/L, mean hemoglobin was 16.9± 3.2 g/dl, mean corpuscular volume (MCV) was 77.2± 13.0 fl and mean corpuscular hemoglobin (MCH) was 25.6± 3.9 pg. This is the very first attempt from Pakistan to screen JAK2-exon 12 mutations in PV patients. We further aim to investigate Jak2 exon 12 mutations in larger number of PV patients to assess their clinical relevance and role in disease onset, progression and transformation.

Keywords: Polycythemia vera, Janus kinase 2, V617F, JAK2 Exon 12 mutations, JAK2 exon 14 mutations