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ABSTRACT: Head and neck melanomas (HNMs) are frequent and have a poorer prognosis than melanomas at other sites. Photoprotection in these locations is difficult. In this population-based study of 279 HNMs diagnosed in a French region between 2004 and 2009, major differences were found between genders. A clearcut, sex-related distribution was found between a "peripheral" area (scalp, forehead, temples, ears, and neck) and a "central" one (other parts of the face), with 56.7% of HNMs being located in the peripheral area in men and 79.3% in the central area in women (P<0.0001). Moreover, HNMs located in the peripheral area occurred on the left side in 57.6% of men and on the right side in 73.1% of women (P=0.009). Peripheral HNMs differed from central HNMs by a higher proportion of invasive tumors, nodular or superficial spreading melanomas, and a lower proportion of lentigo maligna melanomas (LMMs). We hypothesized that this differential distribution between men and women could be explained mostly by a major role of long-term photoprotection by hair and sun exposure in a car. Important public health messages could result from these observations, such as the role of hairstyles in melanoma prevention and the importance of reducing sun exposure in a car, particularly in professional drivers.Journal of Investigative Dermatology advance online publication, 7 February 2013; doi:10.1038/jid.2012.405.
Journal of Investigative Dermatology 02/2013; · 6.31 Impact Factor
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Florent Grange,
Coralie Barbe,
Francois Aubin,
Dan Lipsker,
Florence Granel-Brocard,
Michel Velten,
Sophie Dalac,
François Truchetet,
Catherine Michel,
Audrey Mitschler,
Gwendoline Arnoult,
Antoine Buemi,
Stéphane Dalle,
Philippe Bernard,
Anne-Sophie Woronoff
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ABSTRACT: OBJECTIVE To identify clinical and sociodemographic factors associated with very thick melanoma (VTM) (Breslow thickness, ≥3 mm) in France. DESIGN Retrospective, population-based, case-case study using a survey of cancer registries and questionnaires to practitioners. SETTING Five regions covering 19.2% of the French territory and 8.2 million inhabitants. CASES Cases included all incident melanomas with a Breslow thickness of 3 mm or greater (ie, VTM), diagnosed between January 1 and December 31, 2008, in residents of the study area (Alsace, Bourgogne, Champagne-Ardenne, Franche-Comté, and Lorraine, France), and a randomly selected sample of melanomas thinner than 3 mm. MAIN OUTCOME MEASURES Circumstances of diagnosis, clinical and pathological characteristics of melanomas, and sociodemographic characteristics of patients (age, sex, residence, home and family life conditions, educational level, and smoking habits). RESULTS Among 898 melanomas, 149 (16.6%) were VTMs. Very thick melanomas were more often diagnosed in a general-practice setting than thinner melanomas. The rate of immediate clinical recognition by dermatologists was lower for VTMs than for thinner melanomas. In a multivariate logistic regression analysis, factors associated with VTM were the nodular and acrolentiginous types; the head and neck and lower limb locations; older age; male sex; and being single, separated, divorced, or widowed. When only factors related to patients were taken into account, older age, male sex, and living alone were independent risk factors for VTM. The most significant risk was observed for patients living alone. CONCLUSIONS Intrinsic factors related to the tumor and sociodemographic characteristics of patients contribute to the occurrence of VTM. These factors should be better targeted in future secondary prevention programs.
Archives of dermatology 09/2012; · 4.76 Impact Factor
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Corine Bertolotto,
Fabienne Lesueur,
Sandy Giuliano,
Thomas Strub,
Mahaut de Lichy,
Karine Bille,
Philippe Dessen,
Benoit d'Hayer,
Hamida Mohamdi,
Audrey Remenieras, [......],
Laurence Venat-Bouvet,
Hélène Zattara,
Valérie Chaudru,
Gilbert M Lenoir,
Mark Lathrop,
Irwin Davidson,
Marie-Françoise Avril,
Florence Demenais,
Robert Ballotti,
Brigitte Bressac-de Paillerets
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Eve Maubec,
Valérie Chaudru,
Hamida Mohamdi,
Christophe Blondel,
Patricia Margaritte-Jeannin,
Sébastien Forget,
Eve Corda,
Françoise Boitier,
Stéphane Dalle,
Pierre Vabres, [......], Florent Grange,
Marie-Thérèse Leccia,
Lynda Vincent-Fetita,
Ludovic Martin,
Béatrice Crickx,
Pascal Joly,
Luc Thomas,
Brigitte Bressac-de Paillerets,
Marie-Françoise Avril,
Florence Demenais
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ABSTRACT: BACKGROUND: Features associated with an increased frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations have been identified in families with 3 or more patients with cutaneous melanoma (CM). However, in families with 2 patients with CM, which represent the majority of familial melanoma, these factors have been rarely studied. OBJECTIVE: We investigated association of 3 clinical features with the presence of a CDKN2A mutation in a family by extent of CM family clustering (2 vs ≥3 patients with CM among first-degree relatives in a family). METHODS: We included 483 French families that comprised 387 families with 2 patients with CM (F2 families) and 96 families with 3 or more patients with CM (F3+ families). Three clinical factors were examined individually and in a joint analysis: median age at diagnosis younger than 50 years, and 1 or more patient in a family with multiple primary melanoma or with pancreatic cancer. RESULTS: The frequency of CDKN2A mutations was higher in F3+ families (32%) than in F2 families (13%). Although early age at melanoma diagnosis and occurrence of multiple primary melanoma in 1 or more patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families. LIMITATIONS: The study was not population based. CONCLUSIONS: This study shows that factors associated with CDKN2A mutations differ by extent of CM family clustering. It indicates that, in France, families with 2 patients with CM are eligible for genetic testing especially when there is an early age at CM diagnosis and/or 1 or more patients with multiple primary melanoma.
Journal of the American Academy of Dermatology 07/2012; · 3.99 Impact Factor
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Corine Bertolotto,
Fabienne Lesueur,
Sandy Giuliano,
Thomas Strub,
Mahaut de Lichy,
Karine Bille,
Philippe Dessen,
Benoit d'Hayer,
Hamida Mohamdi,
Audrey Remenieras, [......],
Laurence Venat-Bouvet,
Hélène Zattara,
Valérie Chaudru,
Gilbert M Lenoir,
Mark Lathrop,
Irwin Davidson,
Marie-Françoise Avril,
Florence Demenais,
Robert Ballotti,
Brigitte Bressac-de Paillerets
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ABSTRACT: So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
Nature 12/2011; 480(7375):94-8. · 36.28 Impact Factor
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Eve Maubec,
Peter Petrow,
Isabelle Scheer-Senyarich,
Pierre Duvillard,
Ludovic Lacroix,
Julien Gelly,
Agnès Certain,
Xavier Duval,
Béatrice Crickx,
Valérie Buffard,
Nicole Basset-Seguin,
Pierre Saez,
Anne-Bénédicte Duval-Modeste,
Henri Adamski,
Sandrine Mansard, Florent Grange,
Anne Dompmartin,
Sandrine Faivre,
France Mentré,
Marie-Françoise Avril
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ABSTRACT: To evaluate the efficacy and safety of cetuximab, a monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR), as a first-line monotherapy in patients with unresectable squamous cell carcinoma of the skin (SCCS).
Thirty-six patients received cetuximab (initial dose of 400 mg/m(2) followed by subsequent weekly doses of 250 mg/m(2)) for at least 6 weeks with a 48-week follow-up. The primary end point was the disease control rate (DCR) at 6 weeks (according to Response Evaluation Criteria in Solid Tumors [RECIST] criteria). Secondary end points included best response rate, overall survival, progression-free survival (PFS), and toxicity assessment. Association of treatment efficacy with RAS mutations or FcγR genotypes was investigated.
Median age of the study population was 79 years. DCR at 6 weeks was obtained in 25 of 36 patients (69%; 95% CI, 52% to 84%) of the intention-to-treat population. The best responses were eight partial responses and two complete responses. There were no cetuximab-related deaths. There were three related serious adverse events: two grade 4 infusion reactions and one grade 3 interstitial pneumopathy. Grade 1 to 2 acne-like rash occurred in 78% of patients and was associated with prolonged PFS. One HRAS mutation was identified. Combined FcγRIIa-131H/H and/or FcγRIIIa-158V/V polymorphisms were not associated with the clinical outcomes.
As a first-line treatment in patients with unresectable SCCS, cetuximab achieved 69% DCR. A randomized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option especially in elderly patients. The low frequency of RAS mutations in SCCS makes SCCS tumors attractive for EGFR inhibition.
Journal of Clinical Oncology 08/2011; 29(25):3419-26. · 18.37 Impact Factor
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Annales de Dermatologie et de Vénéréologie 05/2011; 138(5 Suppl 1):H21-4. · 0.72 Impact Factor
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ABSTRACT: To investigate the diagnostic value of commercially available BP230 and BP180-NC16a enzyme-linked immunosorbent assays (ELISAs) in routine practice in patients with bullous pemphigoid (BP).
Single-center retrospective study.
French academic dermatology department.
The study population comprised 138 patients, who were admitted from January 1998 through December 2008.
Sera samples were analyzed by ELISA; clinical and immunopathological data were recorded from the patients' medical charts.
BP230 and BP180-NC16a ELISA scores were evaluated with respect to clinical characteristics (number of blisters, mucosal involvement, localized or generalized disease, and outcome) and routine indirect immunofluorescence (IF).
Of the 138 study patients, 81 (59%) had a positive BP230 ELISA result and 119 (86%) had a positive BP180 ELISA result. There was no relationship between a positive ELISA BP230 result and the disease extent at diagnosis or the presence of mucosal involvement. Serum anti-basement membrane zone autoantibodies (indirect IF) were more frequently detected when the BP230 ELISA result was positive (P < .001). The median anti-basement membrane autoantibody titer as detected by indirect IF was higher in patients with a positive BP230 result (P < .001). The BP180 ELISA result was associated with disease extent at diagnosis as estimated by both the percentage of patients with extensive BP (P = .01) and the mean number of blisters (P = .03) but was not associated with mucosal involvement.
The currently available BP230 ELISA is a reliable although less-sensitive test than BP180 ELISA in BP, and its diagnostic added value compared with BP180 ELISA alone is approximately 5%. Our results support the predominant contribution of the BP230-specific autoantibodies to anti-basement membrane zone antibody titer as detected by indirect IF.
Archives of dermatology 03/2011; 147(3):286-91. · 4.76 Impact Factor
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Florent Grange,
Eve Maubec,
Coralie Barbe,
Jamal Kassouma,
Fabien Vitry,
Hubert Johanet,
Florence Granel-Brocard,
Francoise Boitier,
Angelique Girod,
Benoit Couturaud,
Pierre Saez,
Sebastien Albert,
Annick Le Clainche,
Vincent Descamps,
Marie Francoise Avril
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ABSTRACT: There is no consensus regarding the therapeutic utility of sentinel lymph node biopsy (SLNB) versus that of nodal observation (NO) in melanoma.
To prospectively evaluate a standardized counseling procedure and its effect on patient choices to undergo SLNB or NO.
In four centers, patients with melanoma eligible for SLNB or NO received a complete counseling procedure that included verbal information from dermatologists and surgeons, a detailed information sheet, and a written consent form. Data collected included patient and tumor characteristics, counseling conditions, and specialties of informing doctors. Factors influencing patients' choices were studied using multivariate analysis.
Of 343 consecutive patients, 309 were offered SLNB and NO and received complete verbal and written information from a dermatologist alone (62%) or in association with a surgeon (38%). Approximately half took advice from trusted persons, and half asked for additional time before making a decision; 268 (86.7%) ultimately decided to undergo SLNB. Multivariate analysis showed that older patients, those with a head and neck melanoma, and those informed without a surgeon present were more likely to prefer NO.
This counseling procedure was easily implemented in clinical practice. Patients favored SLNB but were able to understand uncertainties and express preferences.
Dermatologic Surgery 02/2011; 37(2):199-206. · 1.80 Impact Factor
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ABSTRACT: Patients with melanoma (MM) have an increased risk of kidney cancer, and there is an excess risk of MM among patients with renal cell carcinoma (RCC). The objective of the current study was to analyze a series of 42 patients with both MM and RCC to identify clinical and pathologic features as well as risk factors of this association.
Clinical and pathologic characteristics of 42 patients who developed both MM and RCC (the MM + RCC series) were compared with 2 published series in each cancer alone: a series of 293 patients with MM (MM series) and a series of 1527 patients with RCC (RCC series).
RCC was diagnosed concomitantly or after MM in 83% of patients in the MM + RCC series. Those patients displayed a high proportion of asymptomatic RCC at diagnosis (70%) and a higher frequency of stage I tumors (61%) than patients in the RCC series. Compared with the MM series, patients in the MM + RCC series more often were men, had a higher frequency of blond/red hair, had poor tanning ability, and had a higher number of nevi. In addition, patients in the MM + RCC series had a high aggregation of other malignancies (mainly skin cancers) and a significantly higher frequency of family history of MM (P = .005). Only 2 cyclin-dependent kinase 2A gene (CDKN2A) germline mutations were identified among patients in the MM + RCC series who also were members of MM-prone families.
The high aggregation of cancers among patients in the MM + RCC series and the familial clustering of MM argued for a genetic predisposition that may be partly independent of CDKN2A.
Cancer 12/2010; 116(24):5716-24. · 4.77 Impact Factor
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Journal of Investigative Dermatology 05/2010; 130(5):1470-2. · 6.31 Impact Factor
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Frédérique Durbec,
Fabien Vitry,
Florence Granel-Brocard,
Dan Lipsker,
François Aubin,
Guy Hédelin,
Sophie Dalac,
François Truchetet,
Catherine Michel,
Marie-Laure Batard,
Beatrice Domissy-Baury,
Jean-Michel Halna,
Jean Luc Schmutz,
Christian Delvincourt,
Georges Reuter,
Stéphane Dalle,
Philippe Bernard,
Arlette Danzon, Florent Grange
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ABSTRACT: To describe circumstances of the diagnosis and access to dermatological care for patients with cutaneous melanoma (CM) and to investigate factors associated with early detection.
Retrospective population-based study of incident cases of invasive CM in 2004, using questionnaires to physicians and a survey of cancer registries and pathology laboratories.
Five regions in northeastern France.
Six hundred fifty-two patients who were referred to dermatologists by general practitioners (group 1) or by other specialists (group 2), who directly consulted a dermatologist for CM (group 3), or who were diagnosed as having CM during a prospective follow-up of nevi (group 4) or when consulting a dermatologist for other diseases (group 5).
Characteristics of patients, tumors, and patients' residence in each group, including the geographical concentration of dermatologists. We performed multivariate analysis of these factors to determine association with Breslow thickness.
Age, tumor location, Breslow thickness, ulceration, histological type, and geographical concentration of dermatologists significantly differed among groups. Patients consulting dermatologists directly formed the largest group (45.1%). Those referred by general practitioners (26.1%) were the oldest and had the highest frequency of thick (>3 mm), nodular, and/or ulcerated CM. Patients from groups 4 (8.4%) and 5 (14.1%) had the thinnest CMs. Ulcerated and/or thick tumors were absent in group 4. In multivariate analysis, histological types superficial spreading melanoma and lentigo maligna melanoma, younger age, high concentration of dermatologists, and detection by dermatologists were significantly associated with thinner CMs.
Easy access of patients to dermatologists, information campaigns targeting elderly people, and education of general practitioners are complementary approaches to improving early detection.
Archives of dermatology 03/2010; 146(3):240-6. · 4.76 Impact Factor
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ABSTRACT: Hyperthermic isolated limb perfusion (HILP) is a useful therapeutic option in patients with locally advanced melanoma of the extremities. Because HILP allows very high doses of cytotoxic agents to be administered without systemic leakage, the theoretical risk of a secondary malignant neoplasm is real, particularly in the treated limb. Such an event has never been reported to our knowledge, however, possibly in part because survival in these patients is often too short to permit the development of chemo-induced cancers.
We describe 2 cases of secondary rare cancers in 2 elderly women: 1 fatal pleomorphic sarcoma and 1 Merkel cell carcinoma, which developed on the same limb 16 years after HILP for melanoma. The first patient had an exceptional prolonged complete response after HILP for unresectable regional metastases, while the second had been overtreated with HILP and dacarbazine in an adjuvant setting for an early-stage melanoma.
Because long-term survivors of regionally advanced melanoma, although rare, do exist, candidates for HILP should be warned of the risk of long-term development of nonmelanoma secondary cancers. The risk-benefit balance of high-dose local chemotherapy should be carefully evaluated in the light of these findings, especially in patients with early-stage melanoma or other non-life-threatening medical conditions.
Archives of dermatology 03/2010; 146(3):319-21. · 4.76 Impact Factor
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Archives of dermatology 07/2009; 145(6):710-2. · 4.76 Impact Factor
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Philippe Bernard,
Ziad Reguiai,
Emmanuelle Tancrède-Bohin,
Nadege Cordel,
Patrice Plantin,
Christine Pauwels,
Loïc Vaillant, Florent Grange,
Marie-Aleth Richard-Lallemand,
Bruno Sassolas,
Jean-Claude Roujeau,
Catherine Lok,
Catherine Picard-Dahan,
Olivier Chosidow,
Fabien Vitry,
Pascal Joly
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ABSTRACT: To identify prognostic factors for relapse in the first year after cessation of therapy in bullous pemphigoid (BP).
Prospective, multicenter, cohort study (January 1, 2000, through December 31, 2006).
Fifteen French dermatology departments. Patients Patients with BP in remission under low doses of topical or systemic corticosteroids. Interventions Cessation of corticosteroid treatment (day 0) followed by a systematic clinical and immunologic follow-up.
The end point was clinical relapse within the first year after cessation of therapy. Associations of clinical, biological, and immunologic (including direct immunofluorescence, serum anti-basement membrane zone autoantibodies, and serum BP180 autoantibodies by enzyme-linked immunosorbent assay [ELISA] on day 0) variables with clinical relapse were assessed by means of univariate and multivariate analyses.
On day 0, 30 of 114 patients (26.3%) still had a positive result of direct immunofluorescence, 63 of 112 (56.3%) had circulating anti-basement membrane zone autoantibodies, and 34 of 57 (60%) had anti-BP180 antibodies by ELISA. At month 12, 22 patients were dead (n = 11) or lost to follow-up (n = 11), 51 were in remission, and 45 had had relapses (mean interval to relapse, 3.2 months). Factors predictive of relapse within 12 months after cessation of therapy were a positive result of direct immunofluorescence microscopy (P = .02), a greater age (P = .01), and high-titer ELISA scores (P = .02) on day 0. In multivariate analysis, the only factor independently predictive of relapse was a high-titer ELISA score on day 0 (odds ratio, 11.00; 95% confidence interval, 1.29-93.76).
High-titer anti-BP180 ELISA score and, to a lesser degree, a positive direct immunofluorescence finding are good indicators of further relapse of BP. At least 1 of these tests should be performed before therapy is discontinued.
Archives of dermatology 06/2009; 145(5):537-42. · 4.76 Impact Factor
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Florent Grange,
Eve Maubec,
Martine Bagot,
Marie Beylot-Barry,
Pascal Joly,
Stéphane Dalle,
Emmanuel Delaporte,
Olivier Dereure,
Hervé Bachelez,
Béatrice Vergier,
Tony Petrella,
Michel D'Incan
Archives of dermatology 04/2009; 145(3):329-30. · 4.76 Impact Factor
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ABSTRACT: Mycosis fungoides and Sézary syndrome are cutaneous T-cell lymphomas characterized by the epidermotropism of tumor cells. Neuropathic disease is rare during mycosis fungoides and Sézary syndrome and usually results from a central nervous system involvement in late stages. Neurolymphomatosis is defined as the infiltration of the peripheral nerves by tumor lymphocytes. It has been described in patients with aggressive systemic lymphomas but, to our knowledge, not in patients with mycosis fungoides or Sézary syndrome. We report the first case of neurolymphomatosis in a patient with Sézary syndrome and the partial efficacy of high-dose methotrexate sodium in treating this usually refractory complication.
A 73-year-old woman with newly diagnosed Sézary syndrome rapidly developed severe peripheral neuropathic disease with multiple paralyses. Biopsy specimens were taken from a clinically affected nerve and the adjacent muscle; they revealed a neural infiltration by Sézary cells with secondary muscular atrophy. Partial response and major neurologic recovery occurred and persisted under high doses of intravenous methotrexate until the patient died 14 months after the Sézary syndrome diagnosis from a pericarditis of uncertain origin.
This unusual and demonstrative case report highlights the possible neurotropism of malignant cells in Sézary syndrome and suggests the effectiveness of high doses of intravenous methotrexate in this rare and fatal disorder.
Archives of dermatology 04/2009; 145(3):294-6. · 4.76 Impact Factor
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ABSTRACT: We aimed to better characterize exceptional cases of long survivors (LSs) among patients with stage IV melanoma. We performed a comprehensive regional investigation in the Champagne-Ardenne region, France. During the period 1994-2003, 316 patients died of melanoma whereas 10 patients diagnosed with distant metastases had a subsequent survival time > 4 years. These 10 LSs were characterized by a long delay (median: 58 months) prior to distant metastases and by frequent subsequent complete remissions (CRs). Eighteen episodes of CRs, lasting 3-139 months (mean: 26.4), were documented in 9 patients, for single or multiple tumors, for metastases of any site and with any treatment, even including spontaneous CRs. Four of 8 evaluable patients had clinical and/or biological features of auto-immunity. At 31 March 2007, 3 patients had died of melanoma and 1 of a chemo-induced leukaemia. The median survival time was 65 months (range: 52-139). These data suggest that long survival in stage IV melanoma might depend less on the site of metastases and specific therapies than on the patients themselves and their spontaneous antitumor control.
European journal of dermatology: EJD 01/2009; 19(1):38-43. · 2.53 Impact Factor
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F Lesueur,
M de Lichy,
M Barrois,
G Durand,
J Bombled,
M-F Avril,
A Chompret,
F Boitier,
G M Lenoir,
B Bressac-de Paillerets, [......],
Laurence Olivier-Faivre,
Vincent Orlandini,
Pascal Pujol,
Bruno Sassolas,
Dominique Stoppa-Lyonnet,
Luc Thomas,
Pierre Vabres,
Laurence Venat,
Ewa Wierzbicka,
Hélène Zattara
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ABSTRACT: Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.
British Journal of Cancer 08/2008; 99(2):364-70. · 5.04 Impact Factor
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Gaëlle Quereux,
Sonia Marques,
Jean-Michel Nguyen,
Christophe Bedane,
Michel D'incan,
Olivier Dereure,
Elisabeth Puzenat,
Alain Claudy,
Ludovic Martin,
Pascal Joly,
Michele Delaunay,
Marie Beylot-Barry,
Pierre Vabres,
Philippe Celerier,
Bruno Sasolas, Florent Grange,
Amir Khammari,
Brigitte Dreno
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ABSTRACT: To assess the rate of objective response to pegylated liposomal doxorubicin hydrochloride (Caelyx) in patients with advanced or refractory cutaneous T-cell lymphoma (CTCL).
Prospective, open, multicenter study.
Thirteen dermatology departments in France.
Twenty-five patients with either (1) stage II to stage IV CTCL previously unsuccessfully treated with at least 2 lines of treatments or (2) histologically transformed epidermotropic CTCL requiring chemotherapy.
Administration of Caelyx intravenously once every 4 weeks at a dose of 40 mg/m(2).
The response to treatment was evaluated by clinical evaluation.
At the end of treatment, we observed an objective response (primary end point) in 56% of the patients (14 of 25): 5 complete responses and 9 partial responses. The median overall survival time was 43.7 months. For the 14 patients who experienced an objective response, the median progression-free survival time after the end of treatment was 5 months.
This prospective study demonstrates the effectiveness of Caelyx in treating CTCL, with an overall response rate of 56% in spite of the high proportion of patients with advanced-stage disease. Responses were observed in 2 subpopulations of patients in which the prognosis is known to be poorer: Sézary syndrome (overall response rate, 60%) and transformed CTCL (overall response rate, 50%). Moreover, this study shows that dose escalation to 40 mg/m(2) does not seem to improve the effectiveness but increases toxic effects (especially hematologic toxic effects) compared with the dose previously tested of 20 mg/m(2).
Archives of dermatology 07/2008; 144(6):727-33. · 4.76 Impact Factor
