Evidence that superficial basal cell carcinoma is monoclonal from analysis of the Ptch1 gene locus

Saldanha, Gerald; Shaw, Jacqui; Fletcher, A.

doi:10.1046/j.1365-2133.2002.04977.x

Cited by 20 publications

(13 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This suggests that Hh pathway deregulation is likely to be a very early cellular event in BCC. The finding of loss of heterozygosity at chromosome 9q22.3, the PTCH1 locus, in both small and large tumours 31 and clonal loss in multiple independently analysed nests from superficial BCC 32 provides additional support for this proposal. However, the most striking evidence that Hh pathway deregulation is an early event in BCC formation comes from in vivo transgenic model systems.…”

Section: The Hedgehog Pathway and Basal Cell Carcinomamentioning

confidence: 77%

Basal cell carcinoma: a dermatopathological and molecular biological update

2003

Self Cite

View full text Add to dashboard Cite

The ideal classification of basal cell carcinoma (BCC) should be able to identify subtypes which correlate with clinical behaviour and treatment requirements. Unfortunately, however, such a classification has yet to be defined. In the interim, the currently most favoured classification is one based predominantly on histological growth pattern. This classification contributes to the useful concept of low- and high-risk histological subtypes of BCC. The latter are characterized by an increased probability of subclinical extension and/or incomplete excision and/or aggressive local invasive behaviour and/or local recurrence. The Royal College of Pathologists has published a minimum dataset for the histopathological reporting of BCC and this has been written to be compatible with the British Association of Dermatologists' management guidelines. Growth patterns to be reported include nodular, superficial, infiltrative/morphoeic and micronodular types, together with differentiation when of severely atypical or malignant squamous type (basosquamous carcinoma). Deep and peripheral excision margins will be reported to be either involved or clear. The latter will include a comment of a clearance of less than 1 mm for close margins and a measured distance in whole millimetres for other excisions. Clinical assessment and histology remain the 'gold standard' for evaluating BCC and cancers in general. However, in the postgenomic era emphasis is changing from the gathering and archiving of genomic data to its analysis and use in guiding clinical practice. In this context, a current goal is to define cancer phenotype in terms of molecular abnormalities and use this as a new gold standard. One way to assess whether this goal is being achieved for BCC is to determine whether our knowledge of its molecular pathology has any relevance to the minimum dataset for histological reporting. Knowledge of BCC molecular pathology has been fuelled by the recent discovery that deregulation of the Hedgehog (Hh) signalling pathway, a key player in embryonic patterning, appears to be fundamental to tumour growth. But despite accrual of a large amount of data concerning Hh pathway molecular alterations in neoplasia, little is known about the functional consequences of these changes in BCC, how they lead to tumour development, or how they relate to non-Hh pathway alterations such as TP53 mutation. Recent work suggests that the cellular localization of beta-catenin gives a degree of credence to the growth pattern classification of BCC. Furthermore, it is possible that beta-catenin may have a pathogenetic role in the invasive behaviour of BCC. This review draws on current evidence to discuss these issues and assess whether they are relevant to the minimum dataset.

show abstract

Section: The Hedgehog Pathway and Basal Cell Carcinomamentioning

confidence: 77%

Basal cell carcinoma: a dermatopathological and molecular biological update

2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, signature C–T transitions have been found in the homolog of the Drosophila gene PTCH1 (9q22.3) (70,103,104). The PTCH1 gene is the genetic defect of Gorlin’s syndrome, but mutations in the PTCH gene have also been found in 30–40% of sporadic BCC (105).…”

Section: Basic Concepts On Uvr‐associated Bcc Pathogenesismentioning

confidence: 99%

Basal Cell Carcinoma: What’s New Under the Sun

Dessinioti¹,

Antoniou

Katsambas

et al. 2010

Photochem & Photobiology

105

114

View full text Add to dashboard Cite

Basal cell carcinoma (BCC) is the most common skin cancer in white populations with an increasing incidence worldwide, thereby imposing an important public health problem. Its etiology is still unclear, but existing data indicate that the risk for BCC development is of multifactorial origin and results from the interplay of both constitutional and environmental factors. Yet, UV radiation (UVR) is believed to be the predominant causative risk factor in the pathogenesis of BCC. For years, BCC and squamous cell carcinoma (SCC) have been grouped together as ''nonmelanoma skin cancer.'' However, it seems that there are considerable biologic differences between BCC and SCC, and thus each type of epithelial cancer should be addressed separately. The present review provides an overview of the intriguing etiologic link of BCC with UVR and attempts a comprehensive review of recent epidemiologic and molecular evidence that supports this association.

show abstract

“…Genetic alterations include mutations in the p53 and PTCH tumour suppressor genes in about one‐third of BCCs 8,9 . Loss of heterozygosity data for chromosome 9q22.3 ( PTCH1 ) indicate that superficial BCC is monoclonal 10 . In the downstream processes of patched gene inactivation the Gli‐1 transcription factor seems to play an important role 11 .…”

mentioning

confidence: 99%

Risk and protective factors for sporadic basal cell carcinoma: results of a two-centre case-control study in southern Germany. Clinical actinic elastosis may be a protective factor

et al. 2004

View full text Add to dashboard Cite

In contrast to earlier reports, clinical actinic elastosis turned out to be the only protective factor for sporadic BCC. A special relationship between wrinkling and BCC risk could not be shown. For basic research, future work should be aimed at elucidating further the different forms of collagen repair processes after intermittent and/or chronic UV exposure. The data strongly support the recommendation that a change in recreational UV exposure habits in individuals, and sunburn avoidance in particular, are necessary not only because of the increased long-term risk of melanoma, but also because of the risk of other skin cancers such as sporadic BCC.

show abstract

Evidence that superficial basal cell carcinoma is monoclonal from analysis of the Ptch1 gene locus

Abstract: These probabilities were so extreme that it was unlikely that the nests arose independently, thus providing the first molecular evidence that superficial BCC is monoclonal.

Cited by 20 publications

References 19 publications

Basal cell carcinoma: a dermatopathological and molecular biological update

Basal cell carcinoma: a dermatopathological and molecular biological update

Basal Cell Carcinoma: What’s New Under the Sun

Risk and protective factors for sporadic basal cell carcinoma: results of a two-centre case-control study in southern Germany. Clinical actinic elastosis may be a protective factor

Contact Info

Product

Resources

About