Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers

Vivo, Immaculata De; Gertig, Dorota M.; Nagase, Satoru; Hankinson, Susan E.; O’Brien, Rebecca L.; Speizer, Frank E.; Parsons, Ramon; Hunter, David J.

doi:10.1136/jmg.37.5.336

Cited by 49 publications

(20 citation statements)

References 25 publications

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“…The low rate of PTEN mutation among women with an inherited predisposition or early onset of breast cancer is similar to the experience from ethnically diverse populations. De Vivo and co‐workers (22) reported two missense mutations in PTEN in five women from among 103 women with two primary cancer types. Fitzgerald et al.…”

Section: Discussionmentioning

confidence: 99%

Germline mutations in the PTEN gene in Israeli patients with Bannayan–Riley–Ruvalcaba syndrome and women with familial breast cancer

Figer¹,

Kaplan²,

Frydman

et al. 2002

Clinical Genetics

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Germline mutations in BRCA1 or BRCA2 account for the majority of inherited breast cancer cases. Yet, in up to 40% of familial breast cancer cases, no mutations can be detected in either gene. Germline mutations in PTEN underlie two inherited syndromes: Cowden disease (CD) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). The known association of CD with breast cancer risk made it plausible that germline mutations within PTEN may play a role in inherited predisposition to breast cancer. The nine coding exons of the PTEN gene were screened for harboring germline mutations using denaturing gradient gel electrophoresis (DGGE) complemented by sequencing, in two subsets of Israeli patients: 12 patients clinically diagnosed with BRRS, and 89 women with an apparent inherited predisposition to breast cancer, some with salient features of CD. Two of three familial BRRS patients exhibited novel germline mutations in PTEN: a missense mutation changing methionine to arginine at codon 134, and insertion of two nucleotides (CA) at cDNA position 1215 resulting in a frameshift at codon 61 and a premature stop at codon 99. Among 89 high-risk women, two missense mutations were detected in exon 4: A to C change at cDNA position 1279 resulting in a change of aspargine to threonine at codon 82 (N82T), and a G to an A alteration in 1269 which alters threonine to alanine at codon 78 (T78A), a non-conservative missense mutation. This study suggests that PTEN does not play a major role in predisposing to hereditary breast cancer in Israeli women, and that detection of PTEN mutations in BRRS patients is more likely in familial cases.

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Section: Discussionmentioning

confidence: 99%

Germline mutations in the PTEN gene in Israeli patients with Bannayan–Riley–Ruvalcaba syndrome and women with familial breast cancer

Figer¹,

Kaplan²,

Frydman

et al. 2002

Clinical Genetics

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“…Overall, decreased PTEN protein expression correlates with unregulated cellular proliferation. Somatic PTEN deletions and/or mutations occur with a wide distribution of frequencies in sporadic primary tumors, such as endometrial carcinomas, glioblastoma multiform, prostate cancer, breast cancer, and melanomas [De Vivo et al, 2000]. Germ-line PTEN mutations have been identified in patients suffering from CS [Marsh et al, 1998], BRRS [Longy et al, 1998], and Proteus-like syndrome .…”

Section: Discussionmentioning

confidence: 99%

PTEN hamartoma tumor syndromes in childhood: Description of two cases and a proposal for follow‐up protocol

Piccione

Fragapane

Antona

et al. 2013

American J of Med Genetics Pt A

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PTEN hamartoma tumor syndromes (PHTS) are a spectrum of hamartomatous overgrowth syndromes associated with germ‐line mutations in the tumor suppressor PTEN gene located on 10q23.3. It is widely accepted that two of these disorders, Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome, are allelic conditions. Because PTEN mutations are not identifiable in every case of the PHTS phenotype, the inability to detect a mutation within the PTEN gene does not invalidate the clinical diagnosis of Cowden syndrome, or Bannayan–Riley–Ruvalcaba syndrome, in patients who meet diagnostic criteria for these disorders. PTEN mutations are associated with an increased risk for developing breast, thyroid, endometrial, and sometimes renal cancers. Thus, cancer surveillance is the cornerstone of PHTS patient management. Although a consensus cancer surveillance protocol has not been formally instituted, all PTEN mutation carriers should adopt the cancer surveillance strategies proposed for patients with Cowden syndrome. In addition, because gastrointestinal and vascular complications can be more severe in Bannayan–Riley–Ruvalcaba syndrome than in Cowden syndrome, patients with Bannayan–Riley–Ruvalcaba syndrome should be monitored from this point of view too. In this study, we report on two cases with Bannayan–Riley–Ruvalcaba phenotype that showed two different PTEN mutations. We also propose practice recommendations for management of PHTS patients. © 2013 Wiley Periodicals, Inc.

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“…Inherited mutations in genes predisposing for breast cancer (BRCA1, BRCA2, PTEN, p53) increase risks of other cancers also and will therefore contribute to the relative risks of subsequent cancers, particularly for breast cancer diagnosed at a young age (Ford et al, 1994;Eeles, 1995;Breast Cancer Linkage Consortium, 1999;De Vivo et al, 2000). The penetrance for ovarian cancer in 1961-1995 1943-1980 1935-1982 1953-1979 1961-1985 BRCA1 mutation carriers is approximately 0.6 (Easton et al, 1995), compared to the lifetime population risk of 0.013 (RR = 46.15).…”

Section: Discussionmentioning

confidence: 99%

Incidence of multiple primary cancers in a cohort of women diagnosed with breast cancer in southeast England

et al. 2001

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Summary Among women in the Thames Cancer Registry database with a first breast cancer diagnosed between 1961-1995 observed numbers of subsequent cancers were compared with expected numbers and standardized incidence ratios were calculated. The occurrence of breast cancers subsequent to cancers at other sites was also examined. Women diagnosed with breast cancer before age 50 had significantly elevated risks for 9 cancer sites namely, oesophagus, stomach, lung, bone, connective tissue, breast, corpus uteri, ovary and myeloid leukaemia compared with 2 sites (corpus uteri and myeloid leukaemia) in women diagnosed at age 50 and above. Some of these associations are consistent with the effects of known inherited cancer susceptibility genes, shared environmental factors, or therapy.

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Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers

Cited by 49 publications

References 25 publications

Germline mutations in the PTEN gene in Israeli patients with Bannayan–Riley–Ruvalcaba syndrome and women with familial breast cancer

Germline mutations in the PTEN gene in Israeli patients with Bannayan–Riley–Ruvalcaba syndrome and women with familial breast cancer

PTEN hamartoma tumor syndromes in childhood: Description of two cases and a proposal for follow‐up protocol

Incidence of multiple primary cancers in a cohort of women diagnosed with breast cancer in southeast England

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