Deletion mapping of the short arm of chromosome 3 in Merkel cell carcinoma

Leonard, J. Helen; Williams, G.; Walters, Marilyn K.; Nancarrow, Derek J.; Rabbitts, Pamela

doi:10.1002/(sici)1098-2264(199602)15:2<102::aid-gcc4>3.0.co;2-7

Cited by 39 publications

(19 citation statements)

References 21 publications

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“…The mechanism of this risk is not clear but may occur through reduced efficiency of the BER system, alterations of protein–protein interactions or through loss of the wild‐type allele in a classic tumor suppressor model (Knudson PNAS 1971). This latter hypothesis is supported by the observed loss of heterozygosity of the 1p region in CRC35–37 and other cancers 38–41. In addition to the colon, the MUTYH gene is expressed in several tissues including brain, stomach, pancreas, lung, kidney, prostate and endometrium (http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?c=geneid&org=9606&l=4595).…”

Section: Discussionmentioning

confidence: 92%

Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer

Win

Cleary

Dowty

et al. 2011

Intl Journal of Cancer

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Cancer risks for a person who has inherited a MUTYH mutation from only one parent (monoallelic mutation carrier) are uncertain. Using the Colon Cancer Family Registry and Newfoundland Familial Colon Cancer Registry, we identified 2,179 first-and second-degree relatives of 144 incident colorectal cancer (CRC) cases who were monoallelic or biallelic mutation carriers ascertained by sampling population complete cancer registries in the United States, Canada and Australia. Using Cox regression weighted to adjust for sampling on family history, we estimated that the country-, age- and sex-specific standardized incidence ratios (SIRs) for monoallelic mutation carriers, compared to the general population, were: 2.04 (95% confidence interval, CI 1.56–2.70; p < 0.001) for CRC, 3.24 (95%CI 2.18–4.98; p < 0.001) for gastric cancer, 3.09 (95%CI 1.07–12.25; p = 0.07) for liver cancer and 2.33 (95%CI 1.18–5.08; p = 0.02) for endometrial cancer. Age-specific cumulative risks to age 70 years, estimated using the SIRs and US population incidences, were: for CRC, 6% (95%CI 5–8%) for men and 4% (95%CI 3–6%) for women; for gastric cancer, 2% (95%CI 1–3%) for men and 0.7% (95%CI 0.5–1%) for women; for liver cancer, 1% (95%CI 0.3–3%) for men and 0.3% (95%CI 0.1–1%) for women and for endometrial cancer, 4% (95%CI 2–8%). There was no evidence of increased risks for cancers of the brain, pancreas, kidney, lung, breast or prostate. Monoallelic MUTYH mutation carriers with a family history of CRC, such as those identified from screening multiple-case CRC families, are at increased risk of colorectal, gastric, endometrial and possibly liver cancers.

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Section: Discussionmentioning

confidence: 92%

Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer

Win

Cleary

Dowty

et al. 2011

Intl Journal of Cancer

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“…This finding is contrary to a previous study that reported LOH on 3p to be a common abnormality in primary MCC. 37 It seems that primary MCC does not share the deletion on 3p with other similar neuroendocrine carcinomas, that is, SCLC. It has been postulated that chromosome 3p harbors a critical tumor suppressor gene involved in the pathogenesis of human lung cancers.…”

Section: Discussionmentioning

confidence: 99%

Recurrent DNA copy number changes revealed by comparative genomic hybridization in primary Merkel cell carcinomas

et al. 2004

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Comparative genomic hybridization (CGH) was used to search for gains, high-level amplifications and losses of DNA sequences along all chromosome arms in 19 primary Merkel cell carcinomas (MCC). Extensive genetic aberrations, with a mean value of 5.571.1 changes per tumor were detected in 13 out of the 19 samples analyzed. Our CGH results reveal several new and other previously known chromosomal regions that are involved in the pathogenesis of MCC. The majority of the alterations were gains of whole chromosomes or whole chromosome arms. Compared to losses, the frequency of DNA copy number gains was two-fold. DNA sequence copy number gains were most common in chromosomes 6 (42%), 1 (37%), and 5 (32%). The most frequent minimal common regions of gains were 6pterqter (42%), 1q11q31 (32%), and 5p (32%). No recurrent high-level amplifications were observed. High-level amplifications of small chromosomal regions were found in four samples out of the 19 tumors analyzed (21%). Amplifications affected 1q22q24 (5%), 4p (5%), and 5p (5%). Losses most frequently affected chromosomes 13 (21%) and 4 (16%). Minimal common regions with the most frequent losses were 13q13q31 (21%), 4q (16%), and 16q (11%). No significant statistical correlation between genomic aberrations and clinicopathological factors was revealed, despite the fact that there was an obvious tendency towards it. Primary MCC expressing DNA alterations were predominantly distinguished in large tumors, and risk of metastatic dissemination was three-fold compared to tumors with no DNA alterations.

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“…For two patients, samples of both the primary and metastasis were available (MCCd1p, MCCd1m, MCCd3p, and MCCd3m). Tumor samples with a name containing the letter “L” were provided as DNA extracted from flash frozen Australian MCC tumor specimens that are previously described (Leonard et al, 1996). Merkel cell carcinoma diagnoses were made by a dermatopathologist and confirmed with immunohistochemistry and/or with lung imaging to rule out a metastasis originating from a SCLC primary tumor.…”

Section: Materials/methodsmentioning

confidence: 99%

Array-CGH Reveals Recurrent Genomic Changes in Merkel Cell Carcinoma Including Amplification of L-Myc

Paulson

Lemos

Feng

et al. 2009

Journal of Investigative Dermatology

116

107

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Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high-resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10 and 13. MCC tumors with less genomic aberration were associated with improved survival (p=0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26% of tumors, a deletion of 13q14-21 was recurrent in 26% of tumors and contains the well-characterized tumor suppressor RB1, and a novel focal amplification at 1p34 was present in 39% of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, while 4/4 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.

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Deletion mapping of the short arm of chromosome 3 in Merkel cell carcinoma

Cited by 39 publications

References 21 publications

Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer

Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer

Recurrent DNA copy number changes revealed by comparative genomic hybridization in primary Merkel cell carcinomas

Array-CGH Reveals Recurrent Genomic Changes in Merkel Cell Carcinoma Including Amplification of L-Myc

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