Mutations in epidermal growth factor receptor and K-ras in Chinese patients with colorectal cancer

被引:27
作者
Zuo Yunxia [1 ]
Cao Jun [1 ]
Zhu Guanshan [2 ]
Lu Yachao [2 ]
Zhou Xueke [1 ]
Li Jin [1 ]
机构
[1] Fudan Univ, Canc Hosp, Shanghai Med Sch, Dept Med Oncol, Shanghai 200032, Peoples R China
[2] Innovat Ctr China, AstraZeneca Global R& D, Shanghai 201203, Peoples R China
关键词
PREVIOUSLY TREATED PATIENTS; CELL LUNG-CANCER; PHASE-II; PROGNOSTIC INDICATORS; GENETIC ALTERATIONS; SOMATIC MUTATIONS; GEFITINIB; CHEMOTHERAPY; ASSOCIATION; OXALIPLATIN;
D O I
10.1186/1471-2350-11-34
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Mutations of EGFR and K-ras are biomarkers for predicting the efficacy of targeting agents in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). Data on the gene mutation status of EGFR and K-ras in Chinese patients with CRC are limited. Methods: EGFR mutations in exon 18-21 and K-ras mutations in exon 1 and 2 were detected in tumor samples from 101 Chinese patients with CRC by polymerase chain reaction-single strand conformational polymorphism. The relationship between patients' characteristics and survival time and gene mutation status were analyzed using the Statistical Package for the Social Sciences. Results: Only two samples (2.0%) had EGFR mutations in exon 18 or 21, and 33 of 101 samples (32.7%) had K-ras mutations in codon 12, 13, 45, 69, or 80. Univariate analysis suggested that differentiation might be correlated with K-ras mutations (p = 0.05), which was confirmed by a logistic regression model (p = 0.04). The median overall survival (OS) and median survival after metastasis were 44.0 and 18.0 months, respectively, in the mutant K-ras group, and 53.3 and 19.0 months, respectively, in the wild K-ras group. K-ras mutation was not an independent prognostic factor for OS or survival after metastasis (p = 0.79 and 0.78, respectively). Conclusions: In Chinese patients with CRC, EGFR mutations were rare, and K-ras mutations were similar to those of Europeans. New mutations in codons 45, 69, and 80 were found in the Chinese population. Poor differentiation was an independent factor related to K-ras mutations.
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页数:10
相关论文
共 32 条
[1]  
Al-Mulla F, 1998, J PATHOL, V185, P130, DOI 10.1002/(SICI)1096-9896(199806)185:2<130::AID-PATH85>3.0.CO
[2]  
2-M
[3]   Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer [J].
Amado, Rafael G. ;
Wolf, Michael ;
Peeters, Marc ;
Van Cutsem, Eric ;
Siena, Salvatore ;
Freeman, Daniel J. ;
Juan, Todd ;
Sikorski, Robert ;
Suggs, Sid ;
Radinsky, Robert ;
Patterson, Scott D. ;
Chang, David D. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (10) :1626-1634
[4]   Somatic mutations of EGFR in colorectal cancers and glioblastomas [J].
Barber, TD ;
Vogelstein, B ;
Kinzler, KW ;
Velculescu, VE .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (27) :2883-2883
[5]   Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype [J].
Bazan, V ;
Migliavacca, M ;
Zanna, I ;
Tubiolo, C ;
Grassi, N ;
Latteri, MA ;
La Farina, M ;
Albanese, I ;
Dardanoni, G ;
Salerno, S ;
Tomasin, RM ;
Labianca, R ;
Gebbia, N ;
Russo, A .
ANNALS OF ONCOLOGY, 2002, 13 (09) :1438-1446
[6]  
BOS JL, 1990, CANCER RES, V50, P1352
[7]  
BOS JL, 1989, CANCER RES, V49, P4682
[8]   K-RAS MUTATION IN COLORECTAL-CANCER - RELATIONS TO PATIENT AGE, SEX AND TUMOR LOCATION [J].
BREIVIK, J ;
MELING, GI ;
SPURKLAND, A ;
ROGNUM, TO ;
GAUDERNACK, G .
BRITISH JOURNAL OF CANCER, 1994, 69 (02) :367-371
[9]   COMMON MOLECULAR-GENETIC ALTERATIONS IN DUKES-B AND DUKES-C COLORECTAL CARCINOMAS ARE NOT SHORT-TERM PROGNOSTIC INDICATORS OF SURVIVAL [J].
DIX, BR ;
ROBBINS, P ;
SOONG, R ;
JENNER, D ;
HOUSE, AK ;
IACOPETTA, BJ ;
BELL, R ;
CLARKE, G ;
CULLINGFORD, G ;
FAULKNER, K ;
INGRAM, D ;
KERMODE, D ;
KIERATH, A ;
LEVITT, M ;
SMITH, P .
INTERNATIONAL JOURNAL OF CANCER, 1994, 59 (06) :747-751
[10]   Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib [J].
Eberhard, DA ;
Johnson, BE ;
Amler, LC ;
Goddard, AD ;
Heldens, SL ;
Herbst, RS ;
Ince, WL ;
Jänne, PA ;
Januario, T ;
Johnson, DH ;
Klein, P ;
Miller, VA ;
Ostland, MA ;
Ramies, DA ;
Sebisanovic, D ;
Stinson, JA ;
Zhang, YR ;
Seshagiri, S ;
Hillan, KJ .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (25) :5900-5909