Table of Contents
1
UI - 21385665
AU - Marsh DJ; Theodosopoulos G; Howell V; Richardson AL; Benn DE; Proos AL;
TI -
Eng C; Robinson BG
Rapid mutation scanning of genes associated with familial cancer
syndromes using denaturing high-performance liquid chromatography.
SO - Neoplasia 2001 May-Jun;3(3):236-44
AD - Cancer Genetics, Kolling Institute of Medical Research, Royal North
Shore Hospital, St Leonards, Sydney, NSW 2065, Australia.
debbie_marsh@med.usyd.edu.au
Germline mutations in tumor suppressor genes, or less frequently
oncogenes, have been identified in up to 19 familial cancer syndromes
including Li-Fraumeni syndrome, familial paraganglioma, familial
adenomatous polyposis coli and breast and ovarian cancers. Multiple
genes have been associated with some syndromes as approximately 26 genes
have been linked to the development of these familial cancers. With this
increased knowledge of the molecular determinants of familial cancer
comes an equal expectation for efficient genetic screening programs. We
have trialled denaturing high-performance liquid chromatography (dHPLC)
as a tool for rapid germline mutation scanning of genes implicated in
three familial cancer syndromes -- Cowden syndrome (PTEN mutation),
multiple endocrine neoplasia type 2 (RET mutation) and von Hippel-Lindau
disease (VHL mutation). Thirty-two mutations, including 21 in PTEN, 9 in
RET plus a polymorphism, and 2 in VHL, were analyzed using the WAVE DNA
fragment analysis system with 100% detection efficiency. In the case of
the tumor suppressor gene PTEN, mutations were scattered along most of
the gene. However, mutations in the RET proto-oncogene associated with
multiple endocrine neoplasia type 2 were limited to specific clusters or
"hot spots." The use of GC-clamped primers to scan for mutations
scattered along PTEN exons was shown to greatly enhance the sensitivity
of detection of mutant hetero- and homoduplex peaks at a single
denaturation temperature compared to fragments generated using
non--GC-clamped primers. Thus, when scanning tumor suppressor genes for
germline mutation using dHPLC, the incorporation of appropriate
GC-clamped primers will likely increase the efficiency of mutation
detection.
2
UI - 21300310
AU - Stratakis CA
TI -
Clinical genetics of multiple endocrine neoplasias, Carney complex and
related syndromes.
SO - J Endocrinol Invest 2001 May;24(5):370-83
AD - Unit on Genetics and Endocrinology, Developmental Endocrinology Branch,
National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, MD 20892-1862, USA.
stratakc@cc1.nichd.nih.gov
The list of multiple endocrine neoplasias (MENs) that have been
molecularly elucidated is growing with the most recent addition of
Carney complex. MEN type 1 (MEN 1), which affects primarily the
pituitary, pancreas, and parathyroid glands, is caused by mutations in
the menin gene. MEN type 2 (MEN 2) syndromes, MEN 2A and MEN 2B that
affect mainly the thyroid and parathyroid glands and the adrenal
medulla, and familial medullary thyroid carcinoma (FMTC), are caused by
mutations in the REToncogene. Finally, Carney complex, which affects the
adrenal cortex, the pituitary and thyroid glands, and the gonads, is
caused by mutations in the gene that codes for regulatory subunit type
1A of protein kinase A (PKA) (PRKAR1A) in at least half of the known
patients. Molecular defects have also been identified in syndromes
related to the MENs, like Peutz-Jeghers syndrome (PJS) (the STK11/LKB1
gene), and Cowden (CD; the PTEN gene) and von Hippel-Lindau disease
(VHLD; the VHL gene). Although recognition of these syndromes at a young
age generally improves prognosis, the need for molecular testing in the
diagnostic evaluation of the MENs is less clear. This review presents
the newest information on the clinical and molecular genetics of the
MENs (MEN 1, MEN 2, and Carney complex), including recommendations for
genetic screening, and discusses briefly the related syndromes PJS, CD
and VHLD.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
About OncoLink Contact OncoLink Privacy statement Disclaimer Link to OncoLink Home