title: MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines.
abstract: A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (approximately 16%) of the lines, including those derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (approximately 14%) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.
authors.affiliation: Myriad Genetics Inc., Salt Lake City, Utah 84108, USA. tengd@myriad.com
authors.forename: D H
authors.initials: DH
authors.lastname: Teng
authors.forename: R
authors.initials: R
authors.lastname: Hu
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: T
authors.initials: T
authors.lastname: Davis
authors.forename: D
authors.initials: D
authors.lastname: Iliev
authors.forename: C
authors.initials: C
authors.lastname: Frye
authors.forename: B
authors.initials: B
authors.lastname: Swedlund
authors.forename: K L
authors.initials: KL
authors.lastname: Hansen
authors.forename: V L
authors.initials: VL
authors.lastname: Vinson
authors.forename: K L
authors.initials: KL
authors.lastname: Gumpper
authors.forename: L
authors.initials: L
authors.lastname: Ellis
authors.forename: A
authors.initials: A
authors.lastname: El-Naggar
authors.forename: M
authors.initials: M
authors.lastname: Frazier
authors.forename: S
authors.initials: S
authors.lastname: Jasser
authors.forename: L A
authors.initials: LA
authors.lastname: Langford
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: G B
authors.initials: GB
authors.lastname: Mills
authors.forename: M A
authors.initials: MA
authors.lastname: Pershouse
authors.forename: R E
authors.initials: RE
authors.lastname: Pollack
authors.forename: C
authors.initials: C
authors.lastname: Tornos
authors.forename: P
authors.initials: P
authors.lastname: Troncoso
authors.forename: W K
authors.initials: WK
authors.lastname: Yung
authors.forename: G
authors.initials: G
authors.lastname: Fujii
authors.forename: A
authors.initials: A
authors.lastname: Berson
authors.forename: P A
authors.initials: PA
authors.lastname: Steck
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002648:Child; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D014644:Genetic Variation; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D005910:Glioma / Q000235:genetics / Q000473:pathology; D006801:Humans; D007438:Introns; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D017354:Point Mutation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D017384:Sequence Deletion; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human