Somatic mutations of JAK1 and JAK3 in acute leukemias and solid cancers.
OBJECTIVE
The aim of this study was to see whether JAK1, JAK3, and TYK2 genes are altered in human cancers.


METHODS
We analyzed 494 tissues from 186 acute adulthood leukemias, 30 multiple myelomas, and 278 common solid cancers, including 90 breast, 47 gastric, 47 colon, 47 lung, and 47 hepatocellular carcinomas by single-strand conformation polymorphism analysis.


RESULTS
Overall, we found six JAK1 mutations (four in acute leukemias, one in a lung carcinoma, and one in a breast carcinoma) and three JAK3 mutations (two in breast carcinomas and one in a gastric carcinoma). Of note, three JAK1 mutations were an identical p.V658F mutation, which is homologous to JAK2 p.V617F mutation. We also found two other JAK1 mutations that occurred at very close sites (p.T782M and p.L783F). We found three of the four leukemias with JAK1 mutations expressed mutated JAK1 at the mRNA level. For JAK3 mutations, one of them was JAK3 p.V715I that is homologous to the JAK1 p.L783F. These recurrent mutations in identical and homologous sites suggest a possibility that alterations of these amino acids might be important for tumor pathogenesis. With respect to the cancer types, T-acute lymphoblastic leukemia (T-ALL) showed the highest incidence of the mutations (3 of 11; 27.3%).


CONCLUSIONS
Our data indicate that both JAK1 and JAK3 mutations occur in common human cancers and that JAK1 mutation in T-ALL is a frequent event. The data suggest that some of the JAK1 and JAK3 mutations may to be functional and contributes to cancer development, especially to T-ALL development.
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Eun Goo
EG
Jeong
Min Sung
MS
Kim
Hyo Kyung
HK
Nam
Chang Ki
CK
Min
Seok
S
Lee
Yeun Jun
YJ
Chung
Nam Jin
NJ
Yoo
Sug Hyung
SH
Lee
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D053613:Janus Kinase 1 / Q000235:genetics*; D053616:Janus Kinase 3 / Q000235:genetics*; D007938:Leukemia / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D013274:Stomach Neoplasms / Q000235:genetics
C507904:JAK1 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3