Microsatellite instability analysis of bilateral breast tumors suggests treatment-related origin of some contralateral malignancies

Kuligina, Ekatherina Sh.; Grigoriev, M.; Suspitsin, Evgeny N.; Buslov, Konstantin G.; Zaitseva, Olga A.; Yatsuk, Olga S.; Lazareva, Yulia R.; Togo, Alexandr V.; Imyanitov, Evgeny N.

doi:10.1007/s00432-006-0146-0

Cited by 20 publications

(12 citation statements)

References 24 publications

(28 reference statements)

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“…Six MSI cases were detected in ERα, D5S346, and D17S250 markers. Our results showed only low-level MSI, defined as instability at <30-40% of loci when more than 5 markers are used (Kuligina et al, 2007), suggesting that this type of MSI is an event more frequent than high-level MSI (instability at ≥30-40% of loci) in ovarian cancer (Kuligina et al, 2007). In accordance with our results, data reported by Sood et al (2001) also showed that low-level MSI is more frequent than high-level MSI in a study of 109 ovarian tumors.…”

Section: Discussioncontrasting

confidence: 58%

Analysis of microsatellite instability and loss of heterozygosity in ovarian cancer: a study in the population of Espírito Santo, Brazil

Alves¹,

Wolfgramm²,

Neto³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Ovarian cancer is currently the most lethal gynecological malignancy in women. It is a heterogeneous and cytogenetically complex disease previously associated with genomic instability. Our purpose was to analyze microsatellite markers to determine patterns and levels of instability as well as possible correlations with histopathological parameters. Polymerase chain reaction was used to characterize microsatellite instability (MSI) and loss of heterozygosity (LOH) in 24 ovarian tumors at 12 microsatellite loci. A total of 11 samples displayed MSI or LOH. Only low-level MSI was found. Markers D5S346 and CYP11 showed the highest MSI and LOH frequencies. D17S250 LOH was significantly associated with tumor histological type (P = 0.0003), and estrogen receptor α was also associated with tumor histological type (P = 0.048) when a combined analysis of LOH and MSI was performed. Furthermore, LOH was observed in a greater number of markers compared with those displaying MSI. Thus, our results support that MSI is less common than LOH in ovarian cancers.

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Section: Discussioncontrasting

confidence: 58%

Analysis of microsatellite instability and loss of heterozygosity in ovarian cancer: a study in the population of Espírito Santo, Brazil

Alves¹,

Wolfgramm²,

Neto³

et al. 2013

Genet. Mol. Res.

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“…Data from the literature suggest that MSI constitutes a rare event in sporadic breast cancer (0-3%) (Adem et al, 2003;Kuligina et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Evidence for breast cancer as an integral part of lynch syndrome

Bürki

Gautier

Kováč

et al. 2011

Genes Chromosomes & Cancer

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Lynch syndrome, an autosomal dominant cancer predisposition caused by mutations in DNA mismatch repair (MMR) genes, mainly mainly mutL homolog 1, OMIM 120436 (MLH1) and mutS homolog 2, OMIM 609309 (MSH2), encompasses a tumor spectrum including primarily gastrointestinal, endometrial, and ovarian cancer. This study aimed at clarifying the heavily debated issue of breast cancer being part of Lynch syndrome. Detailed clinical data on cancer occurrence in Swiss female MLH1/MSH2 mutation carriers were gathered, all available breast cancer specimens assessed for molecular evidence for MMR deficiency (i.e., microsatellite instability (MSI), MMR protein expression, and somatic (epi)genetic MMR gene alterations) and compiled with the scarce molecular data available from the literature. Seventy unrelated Swiss Lynch syndrome families were investigated comprising 632 female family members at risk of which 92 were genetically verified mutation carriers (52 MLH1 and 40 MSH2). On contrast to endometrial and ovarian cancer, which occurred significantly more often and at younger age in MLH1/MSH2 mutation carriers (median 50.5 and 49.0 years; P < 0.00001), overall cumulative breast cancer incidence closely mirrored the one in the Swiss population (56.5 years). Six (85.7%) of seven breast cancer specimens available for molecular investigations displayed the hallmarks of MMR deficiency. Combined with data from the literature, MSI was present in 26 (70.3%) of 37 and altered MMR protein expression in 16 (72.7%) of 22 breast cancer specimens from MLH1/MSH2 mutation carriers. These findings, thus, provide strong molecular evidence for a pivotal role of MMR deficiency in breast cancer development in Lynch syndrome.

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“…Our recent findings indicate that as many as 1 out of 10 contralateral BCs may de facto be treatment‐induced; in particular, we observed high‐level microsatellite instability (MSI‐H) in 10% of metachronous contralateral carcinomas, but not in other categories of bilateral or unilateral BC. It is not yet clear whether this mutator phenotype results from the direct therapy‐related mutagenic inactivation of mismatch repair genes, or is attributed to positive selection of preexisting MSI‐H clones 19. Furthermore, prolonged adjuvant administration of tamoxifen reduces the incidence of hormone receptor‐positive contralateral tumors, but selects in favor of receptor‐negative metachronous malignancies 20…”

Section: Discussionmentioning

confidence: 99%

Nonrandom distribution of oncogene amplifications in bilateral breast carcinomas: Possible role of host factors and survival bias

Suspitsin

Sokolenko

Togo

et al. 2006

Intl Journal of Cancer

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Amplification of HER2, C-MYC and CCND1 oncogenes is a hallmark of breast cancer (BC); however, its involvement in the bilateral form of this disease has not been investigated yet. In this study, 50 bilateral BC (biBC) pairs (100 tumors) and 72 control unilateral BC were examined using real-time PCR analysis of microdissected archival tissues. In biBC, the frequency of >3-fold oncogene amplification was 6/100 (6%) for HER2, 6/100 (6%) for C-MYC and 7/100 (7%) for CCND1. Altogether, 18/100 (18%) biBC tumors had increased gene dosage of at least one oncogene. Tumors forming synchronous biBC pairs had amplification in 11/46 cases (24%). In 3 of 8 patients with amplification-positive carcinomas, the amplification was detected in both neoplasms: 2 biBC had concordant activation of the same oncogene (HER2 and CCND1, respectively), and in the remaining case distinct oncogenes were affected (HER2 and C-MYC). In contrast, amplifications in metachronous biBC were strongly discordant: none of 27 first carcinomas carried this abnormality, while the frequency of amplification in second tumors (7/27; 26%) was similar to the one observed in unilateral BC (20/72; 28%). The trend toward concordance of oncogene amplification status in synchronous but not in metachronous biBC pairs can be explained by the nearly identical natural history of the disease in simultaneously arising tumors. The skewed pattern of amplifications in metachronous biBC might be attributed to their association with adverse BC prognosis; it appears that only patients with amplification-negative first BC have sufficient chances to survive until the development of the contralateral carcinoma. ' 2006 Wiley-Liss, Inc.

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Microsatellite instability analysis of bilateral breast tumors suggests treatment-related origin of some contralateral malignancies

Cited by 20 publications

References 24 publications

Analysis of microsatellite instability and loss of heterozygosity in ovarian cancer: a study in the population of Espírito Santo, Brazil

Analysis of microsatellite instability and loss of heterozygosity in ovarian cancer: a study in the population of Espírito Santo, Brazil

Evidence for breast cancer as an integral part of lynch syndrome

Nonrandom distribution of oncogene amplifications in bilateral breast carcinomas: Possible role of host factors and survival bias

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