Premium
Frequent allelic imbalance suggests involvement of a tumor suppressor gene at 1p36 in the pathogenesis of human lung cancers
Author(s) -
Nomoto Shuji,
Haruki Nobuhiro,
Tatematsu Yoshio,
Konishi Hiroyuki,
Mitsudomi Tetsuya,
Takahashi Toshitada,
Takahashi Takashi
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/1098-2264(200007)28:3<342::aid-gcc13>3.0.co;2-a
Subject(s) - pathogenesis , suppressor , allele , gene , tumor suppressor gene , cancer research , biology , lung cancer , genetics , immunology , carcinogenesis , medicine , pathology
The short arm of chromosome 1 is among the most frequently affected regions in various types of common adult cancers as well as in neuroblastoma. In a previous study of ours, frequent allelic imbalance at the TP 73 locus at 1p36 was noted in lung cancer despite the absence of TP 73 mutations. This suggested the possible existence of an as yet unidentified tumor suppressor gene on 1p. Our initial attempt using the candidate gene approach did not yield any somatic mutations in the 14‐3‐3σ gene (official gene symbol, SFN ), a mediator of G2 arrest by TP53. Detailed deletion mapping of the telomeric region of 1p was thus carried out as an initial step toward positional cloning. We used seven polymorphic markers in addition to TP 73 to examine 61 primary lung cancers. Allelic imbalance at one or more loci of 1p36 was observed in 30 of the 61 cases, whereas D 1 S 508 at 1p36.2 exhibited the highest frequency (45%) of allelic imbalance among the 1p36 markers examined. In contrast, two proximal markers at 1p32–34 showed significantly less frequent (11–14%) allelic imbalance. Consequently, the present study identified the shortest region of overlap between D 1 S 507 and TP 73, which included the most frequently affected marker, D 1 S 508. In addition, several cases exhibited allelic imbalance confined to a subtelomeric region distal to D 1 S 2845 at 1p36.3. The present findings warrant future studies to identify the putative tumor suppressor gene(s) at 1p36 to gain a better understanding of the molecular pathogenesis of lung cancer. Genes Chromosomes Cancer 28:342–346, 2000. © 2000 Wiley‐Liss, Inc.