PMID- 10079245
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20220408
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 154
IP  - 3
DP  - 1999 Mar
TI  - LKB1 somatic mutations in sporadic tumors.
PG  - 677-81
AB  - Germline mutations of LKB1/Peutz-Jeghers syndrome gene predispose carriers to
      hamartomatous polyposis of the gastrointestinal tract as well as to cancer of
      different organ systems. Although Peutz-Jeghers syndrome patients frequently
      present with neoplasms of the colon, stomach, small intestine, pancreas, breast, 
      ovaries, and cervix, somatic mutations appear to be rare in the sporadic tumor
      types thus far studied (colorectal, gastric, testicular, and breast cancers). To 
      evaluate whether somatic mutations of LKB1 contribute to the tumorigenesis of yet
      unstudied tumor types, we screened 14 cell lines and 129 tumor specimens from
      different cancers for a genetic defect in LKB1. Six melanoma and eight myeloma
      cell lines were scrutinized for LKB1 somatic mutations by genomic sequencing. No 
      changes were found in the coding LKB1 sequence and exon/intron boundaries. Next, 
      we analyzed 12 pancreatic, 8 gastric, 12 ovarian granulosa cell, 26 cervical, 28 
      lung, 24 soft tissue, and 19 renal tumors by single-strand conformational
      polymorphism analysis. Three changes in LKB1 coding nucleotide sequence were
      identified. One base pair deletion at A957 and G958 substitution by T occurred in
      a cervical adenocarcinoma sample, resulting in a frameshift and premature stop
      codon at position 335. Substitution of A581 by T occurred in a lung
      adenocarcinoma sample, resulting in the change of aspartic acid at position 194
      to valine. A loss of another allele was detected in this sample. One silent
      change, C1257T, was found in a pancreatic carcinoma sample. The changes were not 
      present in the matched normal tissue DNA samples. Our results suggest that
      mutational inactivation of LKB1 is a rare event in most sporadic tumor types.
FAU - Avizienyte, E
AU  - Avizienyte E
AD  - Department of Medical Genetics, Haartman Institute, University of Helsinki,
      Finland.
FAU - Loukola, A
AU  - Loukola A
FAU - Roth, S
AU  - Roth S
FAU - Hemminki, A
AU  - Hemminki A
FAU - Tarkkanen, M
AU  - Tarkkanen M
FAU - Salovaara, R
AU  - Salovaara R
FAU - Arola, J
AU  - Arola J
FAU - Butzow, R
AU  - Butzow R
FAU - Husgafvel-Pursiainen, K
AU  - Husgafvel-Pursiainen K
FAU - Kokkola, A
AU  - Kokkola A
FAU - Jarvinen, H
AU  - Jarvinen H
FAU - Aaltonen, L A
AU  - Aaltonen LA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (DNA, Neoplasm)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (STK11 protein, human)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Amino Acid Substitution/genetics
MH  - Base Sequence/genetics
MH  - DNA, Neoplasm/genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation/*genetics
MH  - Neoplasms/*genetics
MH  - Polymorphism, Genetic/genetics
MH  - Polymorphism, Single-Stranded Conformational
MH  - Protein Serine-Threonine Kinases/*genetics
MH  - Tumor Cells, Cultured
PMC - PMC1868601
EDAT- 1999/03/18 00:00
MHDA- 1999/03/18 00:01
CRDT- 1999/03/18 00:00
PHST- 1999/03/18 00:00 [pubmed]
PHST- 1999/03/18 00:01 [medline]
PHST- 1999/03/18 00:00 [entrez]
AID - S0002-9440(10)65314-X [pii]
AID - 10.1016/S0002-9440(10)65314-X [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Mar;154(3):677-81. doi: 10.1016/S0002-9440(10)65314-X.