Identification of a novel candidate gene, CASC2, in a region of common allelic loss at chromosome 10q26 in human endometrial cancer

被引:94
作者
Baldinu, P
Cossu, A
Manca, A
Satta, MP
Sini, MC
Rozzo, C
Dessole, S
Cherchi, P
Gianfrancesco, F
Pintus, A
Carboni, A
Deiana, A
Tanda, F
Palmieri, G
机构
[1] CNR, Ist Chim Biomol, Sez Sassari, I-07040 Sassari, Italy
[2] Univ Sassari, Dipartimento Ostet & Ginecol, Sassari, Italy
[3] CNR, Ist Genet Popol, Santa Maria La Palma, SS, Italy
关键词
endometrial cancer; EC; allelic deletion; positional mapping; cancer; mutation analysis; mRNA expression analysis; CASC2;
D O I
10.1002/humu.20015
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Allelic deletions, which are suggestive for the presence of tumor suppressor genes, represent a common event in endometrial cancer (EC). Previous loss-of-heterozygosity studies for human chromosome 10q identified a candidate deletion interval at 10q25-q26, which we further narrowed to a 160-kb region at 10q26, bounded by markers D10S1236 and WIAF3299. Using a positional candidate approach, we identified three alternative transcripts of a novel human gene, CASC2 (cancer susceptibility candidate 2; formely C10orf5). One of such transcripts, CASC2a, encodes a short protein of 102 amino acids with no similarity to any other known gene product. Three (7%) CASC2a mutations were identified in tumor DNA from 44 EC patients. While c.-156G>Tandc.22C>T(p.Pro8Ser) are sequence variants with unknown functional significance, c.84delA is a mutation with a truncation effect on the predicted protein (p.Asn28fsX50). Expression studies by real-time RT-PCR on several normal and tumor cells revealed that CASC2a mRNA is downregulated in cancer, suggesting that it may act as a potential tumor suppressor gene. The very low mutation rate seems to also indicate that inactivation of CASC2a might probably be due to mechanisms different from genetic alterations. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:318 / 326
页数:9
相关论文
共 30 条
  • [1] Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
    Altschul, SF
    Madden, TL
    Schaffer, AA
    Zhang, JH
    Zhang, Z
    Miller, W
    Lipman, DJ
    [J]. NUCLEIC ACIDS RESEARCH, 1997, 25 (17) : 3389 - 3402
  • [2] Microsatellite instability and mutation analysis of candidate genes in unselected Sardinian patients with endometrial carcinoma
    Baldinu, P
    Cossu, A
    Manca, A
    Satta, MP
    Pisano, M
    Casula, M
    Dessole, S
    Pintus, A
    Tanda, F
    Palmieri, G
    [J]. CANCER, 2002, 94 (12) : 3157 - 3168
  • [3] Bristow Robert E., 1999, Current Opinion in Oncology, V11, P388, DOI 10.1097/00001622-199909000-00012
  • [4] Gurin CC, 1999, CANCER RES, V59, P462
  • [5] Rab11 family interacting protein 2 associates with myosin Vb and regulates plasma membrane recycling
    Hales, CM
    Vaerman, JP
    Goldenring, JR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (52) : 50415 - 50421
  • [6] Genetic pathways in colorectal and other cancers (Reprinted from Eur J Cancer, vol 35, pg 335-351, 1999)
    Ilyas, M
    Straub, J
    Tomlinson, IPM
    Bodmer, WF
    [J]. EUROPEAN JOURNAL OF CANCER, 1999, 35 (14) : 1986 - 2002
  • [7] Cancer epigenetics comes of age
    Jones, PA
    Laird, PW
    [J]. NATURE GENETICS, 1999, 21 (02) : 163 - 167
  • [8] Landscaping the cancer terrain
    Kinzler, KW
    Vogelstein, B
    [J]. SCIENCE, 1998, 280 (5366) : 1036 - 1037
  • [9] PTEN1 is frequently mutated in primary endometrial carcinomas
    Kong, DH
    Suzuki, A
    Zou, TT
    Sakurada, A
    Kemp, LW
    Wakatsuki, S
    Yokoyama, T
    Yamakawa, H
    Furukawa, T
    Sato, M
    Ohuchi, N
    Sato, S
    Yin, J
    Wang, SN
    Abraham, JM
    Souza, RF
    Smolinski, KN
    Meltzer, SJ
    Horii, A
    [J]. NATURE GENETICS, 1997, 17 (02) : 143 - 144
  • [10] Genetic instabilities in human cancers
    Lengauer, C
    Kinzler, KW
    Vogelstein, B
    [J]. NATURE, 1998, 396 (6712) : 643 - 649