LKB1 gene mutations in Japanese lung cancer patients.
Mutation of the LKB1 gene (also known as STK11) is regarded as a cause of Peutz-Jeghers syndrome. In Caucasian patients, LKB1 somatic mutations occur in approximately one-third of lung adenocarcinomas. The aim of the present study was to examine the LKB1 gene in Japanese patients with lung cancer and to evaluate its clinical and pathological implications. We sequenced the LKB1 gene in 22 lung cancer cell lines and 100 Japanese patients with lung cancer (including 81 adenocarcinomas, 14 squamous cell carcinomas and five other histological types) who had undergone curative pulmonary resection. We also determined expression levels of the LKB1 gene by quantitative real-time reverse transcription-polymerase chain reaction and correlated these results with the clinical and pathological features of patients. Among the 22 cell lines, four had mutations and three of these were in adenocarcinoma cells. Of 100 primary lung cancers, only three had LKB1 gene mutations (3%). All of them were male smokers with adenocarcinomas. Hence, when confined to this subset of patients, the mutation frequency was 9% (3/33). No significant correlation was observed between the expression level of LKB1 and patient clinicopathological features. In conclusion, LKB1 gene mutations were relatively rare in Japanese patients with lung cancer compared with Caucasian patients. LKB1 gene mutations appear to be frequent in male, smoking patients of Caucasian origin, in contrast to EGFR or HER2 mutations that are frequent in non-smoking, female patients of Asian origin.
Onozato
Ryoichi
R
Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan.
Kosaka
Takayuki
T
Achiwa
Hiroyuki
H
Kuwano
Hiroyuki
H
Takahashi
Takashi
T
Yatabe
Yasushi
Y
Mitsudomi
Tetsuya
T
D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics; D002277:Carcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
Eur J Cancer. 2004 Jan;40(1):136-41
14687797
Science. 2001 Aug 17;293(5533):1323-6
11509733
J Pathol. 2004 Jun;203(2):645-52
15141379
Br J Cancer. 2003 Jul 21;89(2):308-13
12865922
Cancer Res. 1998 May 15;58(10):2087-90
9605748
Nature. 1998 Jan 8;391(6663):184-7
9428765
Mol Cell. 2001 Jun;7(6):1307-19
11430832
Cancer Res. 2004 Dec 15;64(24):8919-23
15604253
Cancer Res. 1998 Sep 1;58(17):3787-90
9731485
J Med Genet. 2001 Jun;38(6):356-60
11389158
Nat Rev Cancer. 2002 Jul;2(7):529-35
12094239
Jpn J Cancer Res. 1999 Jun;90(6):629-32
10429654
Am J Pathol. 1999 Jun;154(6):1835-40
10362809
Nat Genet. 1998 Jan;18(1):38-43
9425897
Oncogene. 2004 May 20;23(23):4041-9
15048080
Cancer. 2001 Sep 15;92(6):1525-30
11745231
Oncogene. 2007 Aug 30;26(40):5911-8
17384680
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9248-51
10430928
Oncogene. 2003 May 8;22(18):2812-22
12743604
Gastroenterology. 2000 Dec;119(6):1447-53
11113065
Hum Mol Genet. 1999 Jan;8(1):45-51
9887330
J Clin Pathol. 2001 Feb;54(2):126-31
11215281
Oncogene. 2004 May 13;23(22):4037-40
15021901
Clin Cancer Res. 2002 Jul;8(7):2085-90
12114407
Cancer Res. 2002 Jul 1;62(13):3659-62
12097271
Cancer Res. 2003 Mar 15;63(6):1382-8
12649203
J Clin Oncol. 2003 Mar 1;21(5):907-13
12610192
J Thorac Oncol. 2006 Sep;1(7):629-34
17409929
Cancer Res. 2000 Feb 1;60(3):546-8
10676634
Cancer Res. 1992 May 1;52(9 Suppl):2665s-2669s
1562997
N Engl J Med. 2005 Nov 10;353(19):2012-24
16282176
Int J Clin Oncol. 2006 Jun;11(3):190-8
16850125
J Biol Chem. 2001 Aug 31;276(35):32415-8
11445556
Oncogene. 2004 Jun 24;23(29):5084-91
15077168