Identification of a Gene Located at Chromosome 5q21 that Is Mutated in Colorectal Cancers

Abstract

Recent studies have suggested the existence of a tumor suppressor gene located at chromosome region 5q21. DNA probes from this region were used to study a panel of sporadic colorectal carcinomas. One of these probes, cosmid 5.71, detected a somatically rearranged restriction fragment in the DNA from a single tumor. Further analysis of the 5.71 cosmid revealed two regions that were highly conserved in rodent DNA. These sequences were used to identify a gene, MCC ( m utated in c olorectal c ancer), which encodes an 829-amino acid protein with a short region of similarity to the G protein-coupled m3 muscarinic acetylcholine receptor. The rearrangement in the tumor disrupted the coding region of the MCC gene. Moreover, two colorectal tumors were found with somatically acquired point mutations in MCC that resulted in amino acid substitutions. MCC is thus a candidate for the putative colorectal tumor suppressor gene located at 5q21. Further studies will be required to determine whether the gene is mutated in other sporadic tumors or in the germ line of patients with an inherited predisposition to colonic tumorigenesis.

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

“…(iii) Finally, a Kaplan–Meier survival analysis further narrowed down this list to 177 candidate tumor suppressors whose downregulation is negatively correlated with patient survival (and thus, likely to enhance tumor progression; see Materials and Methods, Fig 1A and Table EV3). Reassuringly, the resulting list includes several known colon tumor suppressors such as APC (Fearnhead et al , 2001; Aoki & Taketo, 2007), TCF7L2 (Hazra et al , 2008; Slattery et al , 2008), MCC (Kinzler et al , 1991), PTEN (Nassif et al , 2004; Song et al , 2012), and SMAD4 (Miyaki et al , 1999; Alazzouzi et al , 2005). It also includes 34 metabolic genes that are present in the human metabolic model (Table EV4), and which we further studied in the next modeling step.…”

Rapid generation of region-specific genomic clones by chromosome microdissection: Isolation of DNA from a region frequently deleted in malignant melanoma

“…Tumor suppressor genes (whose inactivation results in the release of a cell from normal growth control) have now been clearly documented to play an important role in the multistep process of malignant transformation (Knudson, 1971;Stanbridge, 1990;Marshall, 1991;Kinzler et al, 1991). Evidence suggesting the presence of tumor suppressor genes comes from several sources in-1 To whom reprint requests should be addressed at Departments of Radiation Oncology and Human Genetics, The University of Michigan Medical School, MSRB II C560, 1150 West Medical Center Dr., Ann Arbor, MI 48109-0668.…”

“…cluding: (1) cytologically recognizable deletion of genomic material (Kinzler et al, 1991;Solomon et al, 1991); (2) evidence of allelic loss (assessed by restriction fragment length polymorphism [RFLP] analysis) (Vogelstein et al, 1989;Millikin et al, 1991); and (3) somatic cell hybridization experiments documenting reversion of tumorigenicity (Stanbridge, 1990;Trent et al, 1990). Nonrandom rearrangements of the long arm of chromosome 6 occur in several malignancies, including malignant melanoma (Mitelman, 1991).…”

Infrequent alterations of the APC and MCC genes in gastric cancers from British patients

“…Inactivation of the tumoursuppressor gene, APC (adenomatous polyposis coli), is thought to be an initiating event (Powell et al, 1992). Germline mutations of the APC gene are responsible for familial adenomatous polyposis (FAP) (Nishisho et al, 1991;Groden et al, 1991). Allele loss of another tumoursuppressor gene, MCC (mutated in colorectal cancer), which lies in close proximity to APC on chromosome 5q22, is also frequent and mutations have been described in some colorectal tumours (Kinzler et al, 1991).…”